muramidase and Respiratory-Tract-Infections

Subsequent to the first report in the 1940s on incubation of tissue sections with fluorescein-conjugated antibodies for localization of antigens, a great number of modifications were introduced to improve the validity of immunohistochemistry which has become a growingly popular tool. The use of immunoenzymatic techniques eliminates the need for expensive fluorescence microscopy equipment, the lack of permanency of preparations and the lack of electron density required in ultrastructural localization of antigens. Regardless of the technique, it is also important to choose a correct fixation which allows the proper preservation of antigens and morphology and the penetration of antibodies through the entire thickness of the preparation. A variety of immunohistochemical techniques have been applied to study several components of the lung, such as collagen, surface active material, lung specific antigens, and enzymes and the detection of tumor markers, immunoglobulins and infectious agents in the respiratory system which is reviewed. The large surface area and the multiplicity of cell types provided by the respiratory tract epithelium of humans for exposure to microbial as well as toxic substances in the environment make this organ system very vulnerable but a good early indicator of adverse health effects. Immunohistochemistry provides valuable information complementary to the immunochemical and biochemical characterization of this barrier.

Topics: Animals; Antibody Specificity; Antigens; Collagen; Endothelium; Environmental Pollutants; Histocytochemistry; Humans; Immunoenzyme Techniques; Lung; Lung Neoplasms; Mixed Function Oxygenases; Muramidase; Peptide Hydrolases; Peptidyl-Dipeptidase A; Pulmonary Surfactants; Respiratory System; Respiratory Tract Infections

The current state of knowledge of lung defenses has been reviewed. First, mechanical factors such as aerodynamic filtration and mucociliary transport were considered. Then, in general terms, the contributions of alveolar macrophages, neutrophils, lymphocytes, and immunoglobulins, and the roles of complement, antiproteases, lysozyme, and fibronectin were examined. Interactions between these components may regulate their effect. Finally, the responses to five specific microorganisms were reviewed to illustrate different aspects of the lung's defenses. Streptococcus pneumoniae was selected as a representative extracellular bacterial pathogen, Mycobacterium tuberculosis as an intracellular bacterial pathogen, Mycoplasma pneumoniae because it elicits significant humoral and cell-mediated immunity, respiratory syncytial virus as an example of a local viral pathogen, and measles as a viral pathogen that causes generalized disease. It was shown that these responses may not always be beneficial for the host. For each of the five infections, recommendations for improving the outcome were made.

Topics: Cilia; Complement System Proteins; Fibronectins; Filtration; Humans; Immunoglobulins; Lung; Lymphocytes; Macrophages; Measles; Mucus; Muramidase; Neutrophils; Phagocytosis; Pneumonia, Mycoplasma; Pneumonia, Pneumococcal; Pneumonia, Viral; Protease Inhibitors; Respiratory Tract Infections; Respirovirus Infections; Tuberculosis, Pulmonary

Topics: Complement System Proteins; Esterases; Humans; Immunoglobulins; Macrophage Migration-Inhibitory Factors; Macrophages; Muramidase; Nasal Mucosa; Protease Inhibitors; Respiratory Tract Infections

To address the increasing incidence of gonorrhoea and antimicrobial resistance, we compared the efficacy of Listerine and Biotène mouthwashes for preventing gonorrhoea among men who have sex with men (MSM).. The OMEGA trial was a multicentre, parallel-group, double-blind randomised controlled trial among MSM, done at three urban sexual health clinics and one general practice clinic in Australia. Men were eligible if they were diagnosed with oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the previous 30 days or were aged 16-24 years. They were randomly assigned to receive Listerine (intervention) or Biotène (control) via a computer-generated sequence (1:1 ratio, block size of four). Participants, clinicians, data collectors, data analysts, and outcome adjudicators were masked to the interventions after assignment. Participants were instructed to rinse and gargle with 20 mL of mouthwash for 60 s at least once daily for 12 weeks. Oropharyngeal swabs were collected by research nurses every 6 weeks, and participants provided saliva samples every 3 weeks, to be tested for Neisseria gonorrhoeae with NAAT and quantitative PCR. The primary outcome was proportion of MSM diagnosed with oropharyngeal N gonorrhoeae infection at any point over the 12-week period, defined as a positive result for either oropharyngeal swabs or saliva samples by NAAT, and the cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit. A modified intention-to-treat analysis for the primary outcome was done that included men who provided at least one follow-up specimen over the 12-week study period. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12616000247471).. Between March 30, 2016, and Oct 26, 2018, 786 MSM were screened and 256 were excluded. 264 MSM were randomly assigned to the Biotène group and 266 to the Listerine group. The analysis population included 227 (86%) men in the Biotène group and 219 (82%) in the Listerine group. Oropharyngeal gonorrhoea was detected in ten (4%) of 227 of MSM in the Biotène group and in 15 (7%) of 219 in the Listerine group (adjusted risk difference 2·5%, 95% CI -1·8 to 6·8). The cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit did not differ between the two mouthwash groups (adjusted risk difference 3·1%, 95% CI -1·4 to 7·7).. Listerine did not reduce the incidence of oropharyngeal gonorrhoea compared with Biotène. However, previous research suggests that mouthwash might reduce the infectivity of oropharyngeal gonorrhoea; therefore, further studies of mouthwash examining its inhibitory effect on N gonorrhoeae are warranted to determine if it has a potential role for the prevention of transmission.. Australian National Health and Medical Research Council.

Topics: Adult; Anti-Infective Agents, Local; Australia; Double-Blind Method; Drug Combinations; Glucose Oxidase; Gonorrhea; Homosexuality, Male; Humans; Lactoperoxidase; Male; Mouthwashes; Multicenter Studies as Topic; Muramidase; Neisseria gonorrhoeae; New Zealand; Respiratory Tract Infections; Salicylates; Sexual and Gender Minorities; Surveys and Questionnaires; Terpenes; Young Adult

The purpose of this study was to examine the effects of a probiotic supplement during 4 mo of spring training in men and women engaged in endurance-based physical activities on incidence of upper respiratory tract infections (URTI) and mucosal immune markers. Sixty-six highly active individuals were randomized to probiotic (n = 33) or placebo (n = 33) groups and, under double-blind procedures, received probiotic (PRO: Lactobacillus salivarius, 2 × 1010 bacterium colony-forming units) or placebo (PLA) daily for 16 wk. Resting blood and saliva samples were collected at baseline and after 8 and 16 wk. Weekly training and illness logs were kept. Fifty-four subjects completed the study (n = 27 PRO, n = 27 PLA). The proportion of subjects on PRO who experienced 1 or more wk with URTI symptoms was not different from that of those on PLA (PRO .58, PLA .59; p = .947). The number of URTI episodes was similar in the 2 groups (PRO 1.6 ± 0.3, PLA 1.4 ± 0.3; p = .710). Severity and duration of symptoms were not significantly different between treatments. Blood leukocyte, neutrophil, monocyte, and lymphocyte counts; saliva IgA; and lysozyme concentrations did not change over the course of the study and were not different on PRO compared with PLA. Regular ingestion of L. salivarius does not appear to be beneficial in reducing the frequency of URTI in an athletic cohort and does not affect blood leukocyte counts or levels of salivary antimicrobial proteins during a spring period of training and competition.

Topics: Adolescent; Adult; Athletes; Colony Count, Microbial; Dietary Supplements; Double-Blind Method; Female; Humans; Immunity, Mucosal; Immunoglobulin A, Secretory; Lactobacillus; Leukocyte Count; Male; Motor Activity; Muramidase; Patient Compliance; Physical Endurance; Probiotics; Respiratory Tract Infections; Saliva; Sports; Young Adult

Tears have attracted interest as a minimally-invasive biological fluid from which to assess biomarkers. Lactoferrin (Lf) and lysozyme (Lys) are abundant in the tear fluid and have antimicrobial properties. Since the eye is a portal for infection transmission, assessment of immune status at the ocular surface may be clinically relevant. Therefore, the aim of this series of studies was to investigate the tear fluid antimicrobial proteins (AMPs) Lf and Lys as biomarkers of mucosal immune status. To be considered biomarkers of interest, we would expect tear AMPs to respond to stressors known to perturb immunity but be robust to confounding variables, and to be lower in participants with heightened risk or incidence of illness. We investigated the relationship between tear AMPs and upper respiratory tract infection (URTI; study 1) as well as the response of tear AMPs to prolonged treadmill exercise (study 2) and dehydration (study 3). Study 1 was a prospective cohort study conducted during the common cold season whereas studies 2 and 3 used repeated-measures crossover designs. In study 1, tear Lys concentration (C) as well as tear AMP secretion rates (SRs) were lower in individuals who reported pathogen-confirmed URTI (

Topics: Adolescent; Adult; Biomarkers; Dehydration; Exercise; Female; Humans; Immunity, Mucosal; Immunocompetence; Lactoferrin; Male; Muramidase; Respiratory Tract Infections; Tears; Young Adult

Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin-binding protein (HBP), lysozyme, and the cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung-transplanted patients. One hundred thirteen BALF samples from 29 lung transplant recipients were collected at routine scheduled bronchoscopies at 3 and 6 months, or on clinical indication. Samples were classified into no, possible, probable, or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme, and cytokines were analyzed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, whereas patients with rejection presented low levels that were comparable to noninfection samples. HBP, IL-1β, and IL-8 were the best diagnostic markers of infection with area under the receiver-operating characteristic curve values of 0.88, 0.91, and 0.90, respectively. In conclusion, HBP, IL-1β, and IL-8 could be useful diagnostic markers of pulmonary infection in lung-transplanted patients.

Topics: Adult; Aged; Antimicrobial Cationic Peptides; Blood Proteins; Bronchoalveolar Lavage Fluid; Carrier Proteins; Cytokines; Female; Follow-Up Studies; Humans; Inflammation Mediators; Lung Transplantation; Male; Middle Aged; Muramidase; Prognosis; Prospective Studies; Respiratory Tract Infections; Young Adult

Treatment of bacterial infections becomes increasingly complicated due to increasing bacterial resistance and difficulty in developing new antimicrobial agents. Emphasis should be laid on improvising the existing treatment modalities. We studied the improved antimicrobial and antibiofilm activity of levofloxacin (LFX) and lysozyme (LYS) in microbiological studies. LFX at sub-minimum inhibitory concentration with LYS eradicated > 85% of preformed biofilm. LFX was actively loaded into the liposomes using pH gradient method and was spray-dried with LYS solution. Percent entrapment of LFX in liposome was > 80% and prolonged cumulative release of 85% LFX at the end of 12 h. In vitro lung deposition study and solid-state characterization for spray dried LFX liposome in combination with LYS (LFX liposome-LYS) was performed. Co-spray dried product had mass median aerodynamic diameter ranging < 5 μm. In pharmacodynamic study, Staphylococcus aureus infected rats were treated with LFX liposome-LYS. Lungs, bronchoalveolar lavage fluid (BALF), and nasal fluid were evaluated for microbial burden. Expression of cytokine levels in BALF and serum were also studied by ELISA. In addition, mRNA expression for lung inflammatory mediators and lung myeloperoxidase activity were carried out. Further, lungs and histological changes were observed grossly. Untreated infected rat lungs demonstrated higher mRNA expression for inflammatory markers, cytokine levels, and microbial load compared to vehicle control. Conversely, LFX liposome-LYS significantly abated these adverse repercussions. Histology findings were also in agreement of above. Acute toxicity study revealed safeness of LFX liposome-LYS. Our findings confirm LFX liposome-LYS exhibited prolonged, improved antibiofilm and antimicrobial efficacy in treating S. aureus infection.

Topics: Administration, Inhalation; Animals; Anti-Bacterial Agents; Biofilms; Drug Therapy, Combination; Levofloxacin; Liposomes; Lung Diseases; Muramidase; Rats; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus

Respiratory infections are common after strenuous exercise, when salivary immunity may be altered. We aim to investigate changes in salivary immunity after a marathon and its relationship with lower respiratory tract infections (LRTI) in healthy non-elite marathon runners.. Forty seven healthy marathon runners (28 males and 19 females) who completed the 42.195 km of the 2016 Barcelona marathon were studied. Saliva and blood samples were collected the day before the marathon and two days after the end of the race. Salivary IgA, antimicrobial proteins (lactoferrin, lysozyme) and chemokines (Groα, Groβ, MCP-1) were determined using ELISA kits in saliva supernatant. Blood biochemistry and haemogram were analyzed in all participants. The presence of LRTI was considered in those runners who reported infectious lower respiratory tract symptoms during a minimum of 3 consecutive days in the 2 weeks after the race.. Eight participants (17%) presented a LRTI during the 2 weeks of follow-up. Higher lysozyme levels were detected after the race in runners with LRTI when compared with those without infection. A decrease in salivary lysozyme, Groα and Groβ levels after the race were observed in those runners who did not develop a LRTI when compared to basal levels. Salivary Groα levels correlated with basophil blood counts, and salivary lysozyme levels correlated with leukocyte blood counts.. LRTI are common after a marathon race in non-elite healthy runners. Changes in salivary antimicrobial proteins and chemokines are related to the presence of LRTI and correlate with systemic defense cells, which suggest an important role of salivary immunity in the development of LRTI in non-elite marathon runners.

Topics: Adult; Chemokines; Female; Humans; Immunoglobulin A; Lactoferrin; Male; Muramidase; Respiratory Tract Infections; Running; Saliva

Consistent, moderate-to-vigorous-intensity exercise has been associated with a lower risk of upper respiratory tract infection (URI). However, the molecular basis for this apparent protection has not yet been fully resolved. Host-derived lipids such as cholesteryl esters (CE) have emerged as important effector molecules of innate defense against infections. Here, we compared antimicrobial CE in nasal fluid before and after moderate-to-vigorous exercise between active and inactive subjects.. Nasal fluid was collected from 14 healthy, recreationally active subjects (32 ± 11 yr, 7 men and 7 women) and 14 healthy, inactive subjects (25 ± 3 yr, 7 men and 7 women) before and after treadmill exercise at 70% heart rate reserve. Nasal fluid was analyzed for lysozyme, cholesteryl linoleate (CL), cholesteryl arachidonate (CA), and albumin (Alb) concentrations.. Baseline concentrations (mean ± SEM, inactive vs active) of lysozyme (117.7 ± 31.1 vs 122.9 ± 15.5 μg·mL), CL + CA (15.3 ± 1.8 vs 26.2 ± 10.05 μg·mL), and Alb (156.6 ± 54.5 vs 126.9 ± 32.8 μg·mL) were similar to previously reported levels and did not differ significantly between study groups. However, postexercise, CL + CA concentration was significantly lower in inactive compared with active subjects (7.8 ± 1.5 vs 20.1 ± 4.8 μg·mL, P = 0.036) dropping below the antimicrobial effective range. Once adjusted to Alb concentrations, the changes were no longer significant, suggesting that plasma transudation accounted for the increased CA + CL concentration postexercise in the active group relative to the inactive group.. Moderate-to-vigorous aerobic exercise acutely decreases the antimicrobial CE response in inactive subjects but does not modify baseline levels of CE between active and inactive subjects. This suggests that compared with active individuals, inactive individuals may be at greater risk for upper respiratory tract infection immediately postexercise.

Topics: Adolescent; Adult; Albumins; Cholesterol Esters; Exercise; Exercise Test; Female; Humans; Immunity, Innate; Male; Muramidase; Nasal Lavage Fluid; Oxygen Consumption; Respiratory Tract Infections; Young Adult

Oreochromis niloticus bred in net cages were supplemented with cell wall of Saccharomyces cerevisiae (Sc) (0.3%) or chromium carbochelate (Cr) (18 mg/kg of feed) or in association (Sc + Cr), for 90 days. After this period, acute inflammation was induced in the swim bladder by inoculation of 3 × 10(8) CFU of inactivated Streptococcus agalactiae, and another group received 0.65% saline solution (control). Twelve, 24, and 48 h after stimulation, the inflammation was evaluated through total and differential counting of accumulated cells, and through leukocyte respiratory burst in the blood, cortisolemia, glycemia and serum lysozyme concentration. The results showed that there were greater total numbers of cells in the exudate of fish inoculated with inactivated bacterium than in those injected with saline solution, with predominance of lymphocytes, thrombocytes, macrophages and granulocytes. Tilapia supplemented with Cr presented increased total numbers of cells with significant accumulation of lymphocytes and reductions in cortisolemia and glycemia, but the different treatments did not have any influence on leukocyte respiratory burst or serum lysozyme concentration. Tilapia supplemented with Sc and the Cr + Sc association did not present significant changes to the variables evaluated, despite higher accumulation of lymphocytes in the inflammatory exudate from fish treated with Sc. The results indicate that tilapia bred in net cages and supplemented with Cr presented higher total accumulation of cells at the inflammatory focus, thus indicating an increase in the inflammatory response induced by the bacterium, probably due to the reduction in cortisolemia and higher glucose consumption. Thus, supplementation with Cr had beneficial action, which facilitated development of acute inflammation induced by the bacterium, but did not affect neither leukocyte respiratory burst in the blood nor serum lysozyme concentration.

Topics: Air Sacs; Animals; Blood Glucose; Chromium; Cichlids; Fish Diseases; Hydrocortisone; Muramidase; Probiotics; Random Allocation; Respiratory Burst; Respiratory Tract Infections; Saccharomyces cerevisiae; Streptococcal Infections; Streptococcus agalactiae

Depressed oral respiratory mucosal immunity and increased incidence of upper respiratory symptoms are commonly reported after bouts of prolonged exercise. The current study observed the impact of a 24-h continuous overnight ultra-marathon competition (distance range: 122-208 km; ambient temperature range: 0-20 °C) on salivary antimicrobial protein responses and incidence of upper respiratory symptoms. Body mass, unstimulated saliva and venous blood samples were taken from ultra-endurance runners (n=25) and controls (n=17), before and immediately after competition. Upper respiratory symptoms were assessed during and until 4-weeks after event completion. Samples were analyzed for salivary IgA, lysozyme, α-amylase and cortisol in addition to plasma osmolality. Decreased saliva flow rate (p<0.001), salivary IgA (p<0.001) and lysozyme (p=0.015) secretion rates, and increased salivary α-amylase secretion rate (p<0.001) and cortisol responses (p<0.001) were observed post-competition in runners, with no changes being observed in controls. No incidences of upper respiratory symptoms were reported by participants. A 24-h continuous overnight ultra-marathon resulted in the depression of some salivary antimicrobial protein responses, but no incidences of upper respiratory symptoms were evident during or following competition. Salivary antimicrobial protein synergism, effective management of non-infectious episodes, maintaining euhydration, and (or) favourable environmental influences could have accounted for the low prevalence of upper respiratory symptoms.

Topics: Adult; alpha-Amylases; Drinking; Energy Metabolism; Female; Humans; Hydrocortisone; Immunity, Mucosal; Immunoglobulin A, Secretory; Male; Muramidase; Physical Endurance; Respiratory Tract Infections; Running; Saliva

Vitamin A deficiency (VAD) alters the phenotype of airway epithelium and attenuates the epithelial defense system, and many studies have reported the association of VAD with respiratory disease. In this study, we investigated changes in submucosal glands (SMG) in a mouse model of VAD. C57BL/6 mice were fed a vitamin A-devoid diet and the others were fed a control diet (1.2 mg retinol/kg). The areas of serous and mucous cells of SMG were measured in 4-, 8-, and 20-wk-old male mice. The volume and lysozyme concentration of glandular secretions were also measured. The 2 groups did not differ in body weight or general morbidity at 3-10 wk of age, although serum retinol concentrations were greater in the control mice than in the VAD mice after 4 wk. Upon histological evaluation, we found that the areal ratio of serous cells:total SMG cells was significantly lower after 8 wk in the VAD mice compared with the control mice, although the total area of SMG did not differ between groups throughout the 20-wk experiment. The number of secretory bubbles did not differ between the groups, but total secretion volume was reduced by 35% in 8-wk-old VAD mice compared with controls. Furthermore, the concentration of lysozyme in secretions from 8-wk-old VAD mice was also less than in controls, compounding the effect of diminished secretion volume. In this study, we found serous cell hypotrophy/hypoplasia and dysfunction in VAD mice, which may contribute to the susceptibility to airway infection linked to VAD.

Topics: Animals; Bodily Secretions; Cell Count; Chemokine CXCL2; Disease Resistance; Down-Regulation; ErbB Receptors; Male; Mice; Mice, Inbred C57BL; Mucus; Muramidase; Phosphorylation; Protein Processing, Post-Translational; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Mucosa; Respiratory Tract Infections; RNA, Messenger; Severity of Illness Index; Up-Regulation; Vitamin A Deficiency

The objective of the present study was to estimate the efficacy of laripront intended for the treatment of inflammatory diseases of the laryngopharynx in the children. Available for the observation were 50 patients aged between 4 and 14 years suffering from the following ENT pathologies: adenoiditis, lacunar tonsillitis, acute laryngitis, chronic tonsillitis, oropharyngeal candidiasis, chronic hypertrophic pharyngitis, atrophic pharyngolaryngitis after the chemical burn of the mouse cavity and laryngopharynx or in the case of gastroesophageal reflux disease. All the patients enjoyed the positive outcome of the treatment that was especially efficacions in the patients with acute pathologies. No adverse effects of the treatment were documented.

Topics: Acute Disease; Adolescent; Anti-Infective Agents, Local; Child; Child, Preschool; Chronic Disease; Dequalinium; Drug Combinations; Drug Monitoring; Drug Synergism; Female; Humans; Hypopharynx; Male; Muramidase; Pain; Respiratory Tract Infections; Tablets; Treatment Outcome

To examine the relationship between upper respiratory illness (URI) incidence with changes in mucosal immunity (saliva immunoglobulin A (s-IgA) and saliva lysozyme (s-Lys)) and training load (TL) in a squad of elite rugby union players.. Timed resting morning saliva samples were taken from players (n = 31) at preselected time points for 11 months. Weekly illness rates and TL were assessed using a Web-based diary and from medical/coaching staff reports.. No significant correlation was found between absolute s-IgA or s-Lys concentrations and URI incidence. Peaks in URI (December and March) were preceded by periods of increased training intensity and reduced game activity. In 23% of all URI episodes, players reported that presence of an illness either reduced activity (14.4%) or felt the need to go to bed (8.6%). When s-IgA concentration was expressed relative to that when in a URI-free state, a 15% reduction (P = 0.08) was observed in individuals who had present URI symptoms. Decreases in absolute s-IgA (December) and s-Lys (November and February) concentrations were associated with a corresponding increase in saliva cortisol (P < 0.05). Lower s-IgA (P < 0.05) and s-Lys concentrations were consistently observed in backs than forwards, whereas URI incidence also differed for player position (3.4 forwards vs 4.3 backs).. Regular monitoring of s-IgA and s-Lys may be useful in the assessment of exercise stress and URI risk status in elite team sport athletes. A combination of alterations in training intensity and seasonal influence is a likely contributor to observed peaks in URI incidence. It is probable that stress-induced increases in cortisol release contribute to reductions in mucosal immunity, which, when lowered, predispose rugby players to increased risk of illness.

Topics: Adult; Athletes; Football; Heart Rate; Humans; Hydrocortisone; Immunity, Mucosal; Immunoglobulin A, Secretory; Incidence; Male; Muramidase; Oxygen Consumption; Respiratory Tract Infections; Saliva; Young Adult

To determine the antimicrobial activity of nisin F against Staphylococcus aureus in the respiratory tract.. The respiratory tract of nonimmunosuppressed and immunosuppressed Wistar rats were colonized with 4 x 10(5) viable cells of S. aureus K and then treated by administering 8192 arbitrary units (AU) nisin F intranasal. Symptoms of pneumonia were detected in the trachea and lungs of immunosuppressed rats that had not been treated with nisin F. The trachea and lungs of immunosuppressed rats treated with nisin F were healthy. No significant differences were recorded in blood cell indices. The antimicrobial activity of low concentrations nisin F (80-320 AU ml(-1)) was slightly stimulated by lysozyme and lactoferrin.. Nisin F inhibited the growth of S. aureus K in the respiratory tract of immunocompromised rats. Treatment with nisin F at 8192 AU proofed safe, as the trachea, lungs, bronchi and haematology of the rats appeared normal.. Nisin F is nontoxic and may be used to control respiratory tract infections caused by S. aureus. This is, however, a preliminary study with an animal model and need to be confirmed with studies on humans.

Topics: Administration, Intranasal; Animals; Bronchi; Drug Interactions; Humans; Immunocompromised Host; Lactoferrin; Lung; Male; Muramidase; Nisin; Pneumonia, Bacterial; Rats; Rats, Wistar; Respiratory Tract Infections; Staphylococcal Infections; Staphylococcus aureus; Trachea

Antimicrobial proteins are important in lung defense and are potential therapeutic agents in chronic airways infection such as seen in cystic fibrosis (CF). In preparation for future clinical studies, we sought (1) to determine levels of three antimicrobial proteins [lactoferrin, lysozyme, and secretory leukoprotease inhibitor (SLPI)] in the CF airway and (2) to examine the relationships between these antimicrobial proteins and airway inflammation and infection. We examined bronchoalveolar lavage fluid (BALF) from 45 individuals with CF and 23 disease control individuals. Airway inflammation was measured through BALF neutrophil counts and neutrophil elastase activity. Infection was assessed through quantitative counts of CF-related bacterial pathogens. BALF lysozyme activity and lactoferrin levels were elevated in individuals with CF compared to controls whereas SLPI levels were not different between the groups. Among the CF subjects, lysozyme activity and lactoferrin increased with age while SLPI decreased with age. Lysozyme activity and lactoferrin concentrations correlated positively with neutrophil counts but not with bacterial colony counts. SLPI levels were inversely related to both neutrophil counts and bacterial colony counts. This study provides information concerning the levels of antimicrobial proteins present in the CF airway that are relevant to future clinical trials of these compounds and demonstrates clear relationships between antimicrobial protein-specific levels and airway inflammation and infection.

Topics: Adolescent; Adult; Biomarkers; Bronchitis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Cystic Fibrosis; Female; Humans; Immunity, Innate; Infant; Lactoferrin; Leukocyte Count; Leukocyte Elastase; Male; Muramidase; Respiratory Tract Infections; Secretory Leukocyte Peptidase Inhibitor; Young Adult

The abundance of lysozyme on mucosal surfaces suggests that successful colonizers must be able to evade its antimicrobial effects. Lysozyme has a muramidase activity that hydrolyzes bacterial peptidoglycan and a non-muramidase activity attributable to its function as a cationic antimicrobial peptide. Two enzymes (PgdA, a N-acetylglucosamine deacetylase, and Adr, an O-acetyl transferase) that modify different sites on the peptidoglycan of Streptococcus pneumoniae have been implicated in its resistance to lysozyme in vitro. Here we show that the antimicrobial effect of human lysozyme is due to its muramidase activity and that both peptidoglycan modifications are required for full resistance by pneumococci. To examine the contribution of lysozyme and peptidoglycan modifications during colonization of the upper respiratory tract, competition experiments were performed with wild-type and pgdAadr mutant pneumococci in lysozyme M-sufficient (LysM(+/+)) and -deficient (LysM(-/-)) mice. The wild-type strain out-competed the double mutant in LysM(+/+), but not LysM(-/-) mice, indicating the importance of resistance to the muramidase activity of lysozyme during mucosal colonization. In contrast, strains containing single mutations in either pgdA or adr prevailed over the wild-type strain in both LysM(+/+) and LysM(-/-) mice. Our findings demonstrate that individual peptidoglycan modifications diminish fitness during colonization. The competitive advantage of wild-type pneumococci in LysM(+/+) but not LysM(-/-) mice suggests that the combination of peptidoglycan modifications reduces overall fitness, but that this is outweighed by the benefits of resistance to the peptidoglycan degrading activity of lysozyme.

Topics: Acetyltransferases; Amidohydrolases; Animals; Bacterial Capsules; Bacterial Proteins; Cell Wall; Female; Humans; Mice; Muramidase; Mutation; Nasopharynx; Neutrophils; Peptidoglycan; Pneumococcal Infections; Respiratory Mucosa; Respiratory Tract Infections; Streptococcus pneumoniae

The Streptococcus pneumoniae LytC lysozyme is responsible for autolysis at 30 degrees C (a temperature close to that of the upper respiratory tract), promotes DNA release in competent cultures, and participates in nasopharyngeal colonization. We show that the virulent pneumococcal TIGR4 strain encodes an active LytC enzyme, in contrast with genome-based predictions.

Topics: Base Sequence; Genome, Bacterial; Humans; Molecular Sequence Data; Muramidase; N-Acetylmuramoyl-L-alanine Amidase; Respiratory Tract Infections; Sequence Alignment; Sequence Homology, Nucleic Acid; Streptococcal Infections; Streptococcus pneumoniae

Children and adolescents aged 4-16 years with the diagnosis of acute respiratory viral infection with long-lasting fever, manifestations of intoxication syndrome, and catarrhal symptoms were examined. In children and adolescents suffering from frequent diseases and presented with acute respiratory viral infection we found disorders in the immune status (depression of the cellular component, helper/suppressor imbalance, suppressed production of IgA and hyperproduction of IgM, decreased concentration of secretory IgA in the saliva) in comparison with children rarely falling ill. The redox potential and lymphocyte cytochrome C content were decreased in adolescents often falling ill, while the content of cytochrome oxidase did not change. A negative multiple correlation (R=6.8, p<0.005) was detected between the decrease in cytochrome C content and NADP/NADPH redox potential and increase in the immunoregulatory index. ATP content in lymphocyte from adolescents frequently falling ill remained 21% decreased during the first 2 weeks after acute respiratory viral infection, while the ATP/ADP ratio was shifted towards dinucleotide, which also indicated disorders in ATP synthesis in lymphocytes.

Topics: Acute Disease; Adenosine Triphosphate; Adolescent; Antibodies, Monoclonal; Case-Control Studies; CD4-CD8 Ratio; Child; Child, Preschool; Cytochrome c Group; Energy Metabolism; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Immunoglobulin M; Leukocyte Count; Luciferases; Muramidase; NAD; NADP; Oxidation-Reduction; Respiratory Tract Infections; Saliva; T-Lymphocytes; T-Lymphocytes, Helper-Inducer

Klebsiella pneumoniae is a common virulent causative agent for pneumonia. Lysozyme has previously been shown to play an important role in nonimmune host defense of the airways. This study was undertaken to assess the role of lysozyme M, the major isoform of lysozyme in mouse lung, in the killing of K. pneumoniae in lysozyme M(-/-) mice and transgenic mice with increased expression of lysozyme (lysozyme(tg) mice). The airways of lysozyme M(-/-) mice maintained in a pathogen-free facility were colonized by Lactobacilli, a component of the oropharyngeal flora. No lactobacilli were detected in the lungs of wild-type (WT) or lysozyme(tg) mice. Twenty-four hours after intratracheal infection with K. pneumoniae, bacterial killing was enhanced 9-fold in lysozyme(tg) mice compared with WT mice and 43-fold compared with lysozyme M(-/-) mice. In survival studies, no lysozyme M(-/-) mice survived beyond 72 hours after infection, whereas 75% of lysozyme(tg) (p < 0.01) and 25% of WT mice survived to 120 hours (p < 0.01). Deficiency of lysozyme M in the lungs increased susceptibility to K. pneumoniae infection, whereas increased expression of lysozyme conferred resistance to infection and enhanced survival.

Topics: Animals; Bronchoalveolar Lavage Fluid; Colony Count, Microbial; Cytokines; Klebsiella Infections; Klebsiella pneumoniae; Lung; Mice; Mice, Knockout; Mice, Transgenic; Muramidase; Respiratory Tract Infections; Survival Rate

Topics: Animals; Klebsiella Infections; Klebsiella pneumoniae; Lung; Mice; Muramidase; Respiratory Tract Infections

The respiratory tract produces a number of molecules that act in the first line of host defense to protect against pathogenic colonization and tissue invasion. Most of the innate antimicrobial activity can be attributed to airway fluid proteins, such as lysozyme, lactoferrin, and secretory leukoproteinase inhibitor, and peptides, such as defensins. Human beta-defensins are cationic antimicrobial peptides with broad and potent microbicidal activity that have been shown to play a role in protecting the healthy lung from infection. To determine the effect of thermal injury on the production of the inducible beta-defensin, human beta-defensin-2 (HBD-2), we measured the concentration of HBD-2 by Western blot analysis in bronchoalveolar lavage samples from the lungs of burned patients with and without inhalation injury. Our data demonstrates an increased amount of HBD-2 in the pulmonary airways with thermal injury compared to normal lung. A further substantial increase in levels was noted in chronic lung conditions.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; beta-Defensins; Biomarkers; Blotting, Western; Bronchoalveolar Lavage Fluid; Burns, Inhalation; Chronic Disease; Humans; Lung; Lung Diseases; Lung Injury; Middle Aged; Muramidase; Respiratory Tract Infections

Nasal polyps frequently appear in patients with cystic fibrosis (CF). The aims of this study were to focus on what problems (symptoms, endoscopic findings, and laboratory correlates) nasal polyps cause the CF patient, and how these correlate to the total health situation of this patient group.. The clinical histories, endoscopic investigations of the nasal cavity, and analyses of nasal lavage fluid of 44 patients with CF complicated with nasal polyposis have been compared with those of 67 CF control subjects. The patients were examined at annual control examinations (with pulmonary tests, working capacity, liver tests, and bacterial and blood tests) from 1995 to 1996 at Stockholm Cystic Fibrosis Center, Huddinge University Hospital. All patients were > 2 years of age. The endoscopic findings were related to the actual pulmonary function, inflammatory blood parameters, colonizing pathogens, antibodies (Staphylococcus aureus and Pseudomonas aeruginosa), and genotype.. The patients with nasal polyps differed with respect to chronic colonization of P aeruginosa in sputum samples and had a higher occurrence of serum antibodies against the same species. The two groups did not differ in pulmonary functions, inflammatory parameters, or genotype. The polyps found were mainly small (within the meatus media) and gave no significant increase in ongoing clinical symptoms such as rhinorrhea, nasal obstruction, or hyposmia. Neither was any significantly marked finding concerning the nose (mucosal swellings, secretion, etc.) made in the polyp patients. The patients with CF scored slightly lower in a smell identification test in comparison with the healthy control group. The nasal lavage fluid was analyzed (in 93 of the 111 patients) for the occurrence of P aeruginosa (by polymerase-chain reaction [PCR]), interleukin [IL]-5, IL-8, and lysozyme. The lysozyme and IL-8 content was equal in the two CF groups but increased in comparison with the healthy control group. P aeruginosa was not detected with PCR in any nasal lavage fluid. No measurable levels of IL-5 in the nasal lavage were found.. There was a higher frequency of chronic colonization of P aeruginosa in the lower respiratory tract in patients with nasal polyps. Otherwise, nonsevere nasal polyposis was not an indicator of lower respiratory tract morbidity in CF patients.

Topics: Adolescent; Adult; Antibodies, Bacterial; Child; Child, Preschool; Cystic Fibrosis; Endoscopy; Female; Humans; Interleukin-5; Interleukin-8; Male; Muramidase; Nasal Lavage Fluid; Nasal Polyps; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Risk Factors; Staphylococcal Infections

To determine the underlying mechanisms for rhinovirus-induced nasal secretions, nasal lavage fluids were analyzed during experimental rhinovirus infections.. Twenty patients with allergic rhinitis and 18 nonallergic control subjects were inoculated with rhinovirus type 39. Nasal lavage was performed before and on days 2 through 7 after viral inoculation, and the lavage fluids were assayed for proteins and mast cell mediators.. The secretion of total protein and both plasma proteins (albumin and IgG) and glandular proteins (lactoferrin, lysozyme, and secretory IgA) increased after rhinovirus inoculation. Analysis of the specific protein constituents revealed that nasal secretions during the initial response to the rhinovirus infection were predominantly due to increased vascular permeability. Allergic subjects tended to have fewer symptoms and more vascular permeability than control subjects, and increased histamine secretion after rhinovirus inoculation was more frequently seen in the allergy group.. Nasal secretions found early in the course of a viral upper respiratory infection are due to increased vascular permeability, whereas glandular secretions predominate later in the infection.

Topics: Adolescent; Adult; Common Cold; Female; Histamine; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Lactoferrin; Male; Mucus; Muramidase; Nasal Mucosa; Respiratory Tract Infections; Rhinovirus; Serum Albumin

With a view of the pathogenesis of chronic bronchopulmonary diseases the interrelations between infections and evolving defense system are of interest, they are perhaps detectable by means of diagnostic bronchoalveolar lavage. We carried out cytodifferentiation, investigated adenosine deaminase activities and interleukin 1 formation of macrophages, determined immunoglobulin concentrations (secretory IgA), lysozyme, alpha 2-macroglobulin, alpha 1-antitrypsin, albumin. Because the cytodifferentiation yields insight into topical inflammatory reactions, shows diagnostic useful informations in single cases and because it is simple to carry out we can recommend it for each bronchological examination. There were no results specific for any disease group for parameters mentioned above.

Topics: Adenosine Deaminase; Adolescent; alpha 1-Antitrypsin; Bronchoalveolar Lavage Fluid; Child; Child, Preschool; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunologic Deficiency Syndromes; Infant; Interleukin-1; Leukocyte Count; Lung Diseases, Obstructive; Macrophages; Male; Muramidase; Respiratory Tract Infections; Serum Albumin

Serum and salivary total IgA, IgG and IgM as well as salivary innate non-immunoglobulin antimicrobial factors (lysozyme, lactoferrin, salivary and leukocyte peroxidase systems) were measured in 13 children prone to recurrent respiratory infections and compared to their age-matched healthy controls. Serum IgG and IgM levels were significantly elevated and salivary IgA remarkably low in infection-prone children as compared to the controls. However, the levels of secretory piece-bearing IgA were about the same in both groups. There were no significant differences between the two groups in serum IgA levels or in any of the non-immunoglobulin factors. The results indicate that low salivary IgA is associated with recurrent respiratory infections.

Topics: Child, Preschool; Disease Susceptibility; Female; Humans; Immunity, Innate; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infant; Lactoferrin; Male; Muramidase; Peroxidases; Respiratory Tract Infections; Saliva

Bronchial secretions obtained during bronchoscopic examination of 60 children suffering from respiratory tract infections were studied for the concentration of immunoglobulins, anti-proteolytic factors, lactoferrin, and lysozyme. Eleven children having bronchial asthma without a history of chronic or recurrent infections of the respiratory tract were designated as a control. The results were analysed in relation to clinical diagnosis (chronic bronchitis, bronchitis, bronchiectasis) or to the local status of bronchial mucosa at the time of bronchoscopy (no inflammation, inflammation, inflammation with documented bacterial infection). The statistical analysis of the results revealed a decrease of lactoferrin and locally produced IgA in the group of children suffering from bronchitis and chronic bronchitis. Samples infected with Haemophilus species had significantly higher concentration of lactoferrin than any other group. Similarly, albumin in this group was higher than in the other group except that other bacteria were present. Samples infected with Haemophilus also had increased concentrations of S-IgA, IgG, and anti-proteolytic factors when compared with the group without local inflammation.

Topics: Bacterial Infections; Bronchi; Bronchitis; Child; Child, Preschool; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Lactoferrin; Mucus; Muramidase; Respiratory Tract Infections; Serum Albumin

Topics: Adolescent; Bronchi; Child; Child, Preschool; Cystic Fibrosis; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Muramidase; Respiratory Tract Infections; Saliva

The capacity of fungi belonging to the genus Candida to produce lysozyme was studied. All 60 strains under study were found to possess pronounced muramidase activity. Among these cultures highly active lysozyme producers were discovered, which would make it possible to use them for production purposes in future.

Topics: Candida; Candida albicans; Humans; Muramidase; Respiratory Tract Infections

Topics: Acute Disease; Adolescent; Child; Humans; Mucus; Muramidase; Nasal Mucosa; Respiratory Tract Infections; Saliva; Virus Diseases

Topics: Animals; Cystic Fibrosis; Fatty Acids, Essential; Lung; Macrophages; Microscopy, Electron; Muramidase; Pseudomonas Infections; Pulmonary Alveoli; Rabbits; Respiratory Tract Infections; Staphylococcal Infections

Topics: Bacterial Infections; Humans; Immunoglobulin A, Secretory; Muramidase; Respiratory Tract Infections; Sputum

Topics: Animals; Bacterial Infections; Bacteriolysis; Bronchi; Female; Muramidase; Rats; Rats, Inbred Strains; Respiratory Tract Infections; Tissue Distribution

Topics: Adult; Complement System Proteins; Erythrocyte Count; Humans; Influenza, Human; Leukocyte Count; Muramidase; Mycoplasma Infections; Respiratory Tract Infections

Bronchial secretions from 207 children suffering from various pulmonary diseases and from 15 healthy controls were tested concentration of IgA, IgG, lactoferrin and lysozyme. The results obtained suggest that in many cases of chronic lung diseases in children the levels of lactoferrin and immunoglobulins, especially secretory IgA, are very low. In severe infections (cystic fibrosis, bronchiectases) significant increase of IgG concentration was observed.

Topics: Adolescent; Bronchi; Bronchiectasis; Bronchitis; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Lactoferrin; Lactoglobulins; Muramidase; Recurrence; Respiratory Tract Diseases; Respiratory Tract Infections

Topics: Animals; Body Temperature; Copper; Disease Models, Animal; Lung; Macrophages; Male; Mice; Muramidase; Organ Size; Orosomucoid; Q Fever; Respiratory Tract Infections; Spleen; Time Factors; Zinc

Topics: Communicable Diseases; Humans; Infant, Newborn; Infant, Newborn, Diseases; Meningitis; Muramidase; Otitis; Respiratory Tract Infections

The amount of immunoglobulins A and G and lysozyme in bronchial secretions of children with pneumonia was higher than in ones of bronchitis and infected asthma patients. Immunoglobulins levels increased also with the age of patients.

Topics: Acute Disease; Bronchi; Child; Humans; Immunoglobulin A; Immunoglobulin G; Muramidase; Respiratory Tract Infections

Topics: Acute Disease; Adult; Animals; Anti-Bacterial Agents; Child; Culture Techniques; Dose-Response Relationship, Drug; Drug Synergism; HeLa Cells; Humans; Infant, Newborn; Influenza, Human; Mice; Middle Aged; Muramidase; Respiratory Syncytial Viruses; Respiratory Tract Infections; Respirovirus

Topics: Age Factors; Antigen-Antibody Reactions; Child; Child, Preschool; Complement System Proteins; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Muramidase; Pneumonia; Properdin; Respiratory Tract Infections

Topics: Animals; Cyclophosphamide; Immunosuppressive Agents; Lung; Muramidase; Rabbits; Rats; Respiratory Tract Infections

Topics: Child; Complement System Proteins; Enterovirus Infections; Humans; Muramidase; Respiratory Tract Infections; Virus Diseases

Topics: Bacitracin; Humans; Mouth Diseases; Muramidase; Papain; Respiratory Tract Infections

Topics: Erythromycin; Humans; Muramidase; Respiratory Tract Infections; Tetracycline