lactoferrin and Neutropenia

Complement (C) activation, neutropenia, and mild pulmonary dysfunction attend hemodialysis (HD) with cellophane [for example, cuprophan (Cu)] membranes. While usually asymptomatic, these phenomena may cause distress in patients with cardiopulmonary disease, and "start-up" symptoms of HD might be mediated by C-stimulated granulocytes (PMNs). Cellulose acetate (CA) hemodialysis membranes have been devised and claimed more blood compatible than Cu. In a blinded series of HD patients, pruritus, fatigue, and sense of well-being were each scored statistically more favorably by the patients during HD with CA than during HD with Cu (P less than 0.05). Postulating that less C activation might underlie the benefit, we showed that neutropenia was less severe with CA (nadir 77.6% of initial count, +/- 4 SEM) than with Cu (38.3% +/- 2.9; P less than 0.01). In vitro, incubation of CA membranes with plasma led to less C3 conversion (20% vs. 40%), less PMN aggregating activity (5.9 ZAP units vs. 36.3) and less decrement in CH50 (6.5% vs. 22%) than like incubations of Cu. C activation was also less potent in vivo: During HD plasma C3a rose from a mean 401 ng/ml to a peak 6,325 in patients on Cu dialyzers, but from 426 to only 3,637 in patients on CA devices (P less than 0.05). Time-course studies suggested CA was initially as potent an activator as Cu but rapidly lost ability to activate C, possibly because of saturation of C3b binding sites. As an index of PMN activation, we also assayed plasma lactoferrin and found levels significantly higher during Cu than CA dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anaphylatoxins; Biocompatible Materials; Cellulose; Complement Activation; Complement C3; Complement C3a; Complement C5; Complement C5a; Fatigue; Humans; Kidneys, Artificial; Lactoferrin; Lymphocyte Activation; Membranes, Artificial; Neutropenia; Neutrophils; Prospective Studies; Pruritus; Renal Dialysis; Time Factors

The treatment of children affected by severe congenital neutropenia (SCN) with G-CSF strongly reduces the risk of sepsis by reversing neutropenia. However, SCN patients who respond to the treatment with the growth factor still have an elevated risk of succumbing to sepsis. Because the disease is usually caused by heterozygous mutations of ELA2, a gene encoding for neutrophil elastase (NE), we have investigated in G-CSF-responder and nonresponder patients affected by SCN the expression of polypeptides that constitute the antimicrobial machinery of these cells. In peripheral blood-derived neutrophils of patients with heterozygous mutations of ELA2 who were treated with G-CSF, NE was nearly absent as detected by immunofluorescence and immunoblotting, suggesting that production of the mutant protein interferes with normal gene expression. This defect was associated with abnormal expression of other granule-associated proteins such as myeloperoxidase, lactoferrin, cathepsin G, and human-neutrophil-peptide. Moreover, in one patient with partial response to G-CSF, we observed an impairment of neutrophil antimicrobial activity against Candida albicans, and, to a lower extent against Escherichia coli. Thereby, we propose that the treatment with G-CSF is not sufficient to correct all of the functional deficiency of neutrophils, and this might account for the consistent risk of infections observed in SCN patients.

Topics: Candida albicans; Cathepsin G; Cathepsins; Escherichia coli; Granulocyte Colony-Stimulating Factor; Humans; Infant; Infant, Newborn; Lactoferrin; Leukocyte Elastase; Mutation; Neutropenia; Neutrophils; Peptides; Peroxidase; Sepsis; Serine Endopeptidases

Because the human lactoferrin-derived peptide, hLF(1-11), exerts potent in vitro candidacidal activity, we investigated whether it displays antifungal activity against disseminated Candida albicans infections.. Neutropenic mice were intravenously infected with C. albicans and, 24 h later, were injected with hLF(1-11); 18 h later, the number of viable yeasts in the kidneys was determined microbiologically, the size and number of infectious foci were determined histologically, and serum cytokine levels were determined by immunoassays.. hLF(1-11) was effective (maximum reduction, 1.5 logs) against disseminated C. albicans infections, and its antifungal activity leveled off at a concentration of 0.4 ng of hLF(1-11)/kg of body weight. The antifungal activity of hLF(1-11) was increased in mice injected with interleukin (IL)-10 neutralizing antibodies, which suggests that IL-10 reduces the antifungal activity of hLF(1-11). In agreement with this result was the finding that injection of high doses of hLF(1-11) into infected mice was accompanied by increased levels of IL-10 in serum. Microscopic analysis revealed that infectious foci in kidneys of hLF(1-11)-treated mice contained mainly blastoconidia, whereas filamentous forms were abundant in untreated mice. The peptide inhibited the in vitro morphological transition of C. albicans, in a dose-dependent manner. : hLF(1-11) is effective against disseminated C. albicans infections; and its effects on C. albicans viability and virulence and on host cells may explain this antifungal activity.

Topics: Animals; Antifungal Agents; Candida albicans; Candidiasis; Carrier Proteins; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Female; Fluconazole; Humans; Interleukin-10; Kidney Diseases; Lactoferrin; Mice; Neutropenia; Specific Pathogen-Free Organisms

Cyclophosphamide (CP) is used in the treatment of autoimmune disorders and leukemia. The compound induces severe leuko- and neutropenia. Lactoferrin (LF) is a protein which plays a role in the innate immunity. In this study we evaluated the usefulness of LF in reversing CP-induced lympho- and neutropenia in mice.. CBA mice were treated with CP (350 mg/kg body weight, intraperitoneally) and given LF as a 0.5% addition to drinking water. Alternatively, LF was administered orally (seven doses, 1 mg each) on alternate days following CP injection. Control groups received CP or LF only. Blood samples were taken before treatment and on days 4, 8, 15 and 22 following CP injection to determine leukocytosis and cell types in blood smears.. Mice treated with CP showed severe leukopenia, strong eosinophilia (day 4), and an altered lymphocyte/neutrophil ratio (days 8-22). Treatment of mice with LF for 21 days partially normalized the cell composition in CP-treated mice (increased percentage of lymphocytes and decreased eosinophil content). The content of leukocytes increased upon LF treatment on days 4, 8, 15 and 22 (by 36.8, 39.5, 72 and 70.7%, respectively). More importantly, LF partly normalized the neutrophil and lymphocyte composition on day 22 (neutrophils: 29.2% in control mice, 50.6% in CP-treated, and 39.16% in CP/LF-treated; lymphocytes: 66.18% in control mice, 35% in CP-treated and 48.8% in CP/LF-treated). Administration of LF alone did not change the cell numbers or composition.. LF given orally to CP-immunocompromised mice accelerates reconstitution of lymphopoiesis and myleopoiesis.

Topics: Animals; Body Weight; Cyclophosphamide; Eosinophils; Immunosuppressive Agents; Lactoferrin; Leukocytosis; Lymphocytes; Lymphopenia; Mice; Mice, Inbred CBA; Myelopoiesis; Neutropenia; Neutrophils; Time Factors

We hypothesized that systemic release of endogenous leukocyte-derived polypeptide antimicrobial defensins (polymorphonuclear leukocyte-specific) and lactoferrin (polymorphonuclear leukocyte and epithelial cell derived) occurs in nonneutropenic children with severe sepsis.. We performed a prospective cross-sectional and longitudinal study in a university children's hospital pediatric intensive care unit. Ninety-two consecutive children meeting criteria for sepsis and 14 critically ill children without sepsis (controls) were enrolled, and plasma defensins and lactoferrin concentrations were measured on Days 1 and 3 of sepsis.. Nonneutropenic sepsis patients (n = 71) had increased defensins and lactoferrin plasma concentrations compared with critically ill control patients [defensins, 450 ng/ml vs. 150 ng/ml; lactoferrin, 332 ng/ml vs. 176 ng/ml (median values); P < 0.05] and neutropenic sepsis patients [n = 21; defensins, 450 ng/ml vs. 50 ng/ml; lactoferrin, 332 ng/ml vs. 20 ng/ml (median values); P < 0.05]. Neutropenic sepsis patients had similar plasma defensin concentrations and a decrease in plasma lactoferrin concentrations compared with control patients (P < 0.05). Defensins and lactoferrin plasma concentrations correlated to total white blood cell and absolute neutrophil count (P < 0.05). There was no association between plasma defensin concentration and organ failure or outcome; however, increased plasma lactoferrin concentrations were observed with the development of organ failure (P < 0.05).. These data suggest that increased circulating defensins and lactoferrin release are dependent in part on neutrophil count and might play a role in host defense in children with severe sepsis.

Topics: Adolescent; Child; Child, Preschool; Cross-Sectional Studies; Defensins; Female; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Lactoferrin; Male; Neutropenia; Prospective Studies; Sepsis; Severity of Illness Index

Ex vivo expanded CD34+ progenitor cells from fresh or cryopreserved primate bone marrow, induced to granulocytic differentiation with growth factors, were investigated to determine whether myeloid cells produced in liquid cultures have the normal biologic functions needed for the treatment of patients with neutropenia following high-dose chemotherapy or therapeutic or accidental radiation exposure. Human and simian (baboons or macaques) CD34+ cells were cultured with granulocyte-colony stimulating factor (G-CSF), stem cell factor (SCF), interleukin-1 (IL-1), IL-3, and IL-6, and assessed at 14 days of culture for their capacity to respond to different functional tests. Immunostaining revealed that human ex vivo expanded cells contained myeloperoxydase (MPO, 82% +/- 8%) and lactoferrin (LF, 30% +/- 6%) in their granules. Maturation of cultured cells was associated with stimulated chemotactic responsiveness and respiratory burst activity (superoxide anion and hydrogen peroxide production) in expansions from human, baboon, and macaque CD34+ progenitor cells. Mature cells obtained from ex vivo expansion of selected cryopreserved human bone marrow CD34+ cells presented reduced but significant functional activities (chemotactic responsiveness and hydrogen peroxide production) when compared with human peripheral blood neutrophils. The validation of nonhuman primate ex vivo expansion systems may permit their use as models of irradiation. The feasibility of ex vivo expansion from cryopreserved bone marrow cell samples may offer considerable opportunity for banking bone marrow for autologous transfusion.

Topics: Anemia, Aplastic; Animals; Antigens, CD34; Cells, Cultured; Chemotaxis, Leukocyte; Cryopreservation; Feasibility Studies; Hematopoietic Stem Cells; Humans; Hydrogen Peroxide; Lactoferrin; Macaca fascicularis; Neutropenia; Papio; Peroxidase; Superoxides

Neutropenia and degranulation of neutrophils during hemodialysis with cellulosic membranes have been linked to complement activation, whereas in the synthetic polymethyl methacrylate (PMMA) membrane, degranulation occurs without notable complement activation. The mechanisms of neutrophil degranulation under these conditions have not yet been elucidated. Ionized calcium is an important prerequisite of granulocyte activation during in vitro blood contact with both types of artificial surfaces. This study compared the effect of normal ionized calcium during heparin anticoagulation with the effect of extracorporeal calcium depletion during regional citrate anticoagulation on activation of blood components. Because ionized calcium is reduced only in the extra-corporeal circuit, citrate anticoagulation in addition helps to differentiate between extracorporeal and systemic activation phenomena. Twelve chronic hemodialysis patients were dialyzed with polymethyl methacrylate (PMMA, 16 treatments) or cuprophane (CUP, 16 treatments) membranes either during regional citrate anticoagulation or while anticoagulated with heparin. During hemodialysis with CUP, anticoagulation with citrate significantly reduced neutropenia, C3a levels, and lactoferrin release. Elastase concentrations, however, were not reduced by citrate, probably because elastase release occurred not locally in the cuprophane dialyzer, but mostly in the systemic circulation of the patient. PMMA did not elevate C3a levels, and neutropenia was only mild. Both parameters were not influenced by citrate anti-coagulation. However, PMMA profoundly induced elastase and lactoferrin release during heparin anti-coagulation. Depletion of ionized calcium markedly reduced PMMA-mediated neutrophil degranulation in the extracorporeal circuit. The results indicate that ionized calcium is a requirement for neutrophil degranulation during hemodialysis. In PMMA membranes, neutrophil degranulation occurs independent of high complement levels, occurs at least partially inside the dialyzer, and requires the presence of ionized calcium in the extracorporeal circuit. In cuprophane membranes, degranulation was uncoupled from neutropenia and did not correlate with the degree of complement activation. Even in cuprophane dialysis, degranulation of secondary granules was markedly dependent on ionized calcium levels in the extracorporeal circuit.

Topics: Anticoagulants; Blood Cell Count; Calcium; Cell Degranulation; Citrates; Citric Acid; Complement Activation; Female; Granulocytes; Humans; Lactoferrin; Leukocyte Elastase; Male; Middle Aged; Neutropenia; Neutrophils; Pancreatic Elastase; Renal Dialysis

Levels of plasma lactoferrin are decreased in HIV-1-infected patients in relation to the progression of the disease. Plasma lactoferrin concentrations were determined using a specific and sensitive enzyme immunoassay. 97 plasma were studied (22 asymptomatic, 45 symptomatic patients compared to 30 healthy controls) and the results showed a highly significant decrease (p < 0.001) of the level of lactoferrin in HIV-1-infected patients (respectively 2.79 +/- 1.2 and 0.68 +/- 0.22 micrograms/ml) compared to controls (4.37 +/- 0.83 micrograms/ml). Since it is well established that plasma lactoferrin level could be influenced by the number of neutrophils, the experiments were reproduced in neutropenic patients who represent 10% of recruitment (6 among 45 symptomatic patients). The plasma from neutropenic symptomatic patients (neutrophils < or = 1,300/mm3) showed their mean lactoferrin level at 0.36 micrograms/ml still far above the normal values. In view of the different reported biological effects of lactoferrin that are of great importance in the non-specific defences, the real biological place of the lack of such a molecule could be one important component of the multifactorial nature of HIV-1 infection.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; CD4 Lymphocyte Count; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; HIV Seropositivity; HIV-1; Humans; Lactoferrin; Male; Neutropenia

Plasma lactoferrin content was measured before and after therapy with recombinant granulocyte-macrophage colony-stimulating factor in five patients with aplastic anaemia, six with myelodysplasia, and three with prolonged, severe, chemotherapy-induced neutropenia. Before therapy plasma lactoferrin content was uniformly low. However, patients with aplastic anemia and those with chemotherapy-induced neutropenia had a normal lactoferrin:neutrophil ratio. The low levels of plasma lactoferrin thus reflected the low granulocyte mass. On the other hand, patients with myelodysplasia also had reduced lactoferrin:neutrophil ratios, suggesting qualitative/quantitative abnormalities of neutrophil lactoferrin production. After treatment with granulocyte-macrophage colony-stimulating factor, plasma lactoferrin levels increased in patients with aplastic anemia and in those with chemotherapy-induced neutropenia who showed a neutrophil response to treatment. In these patients, the lactoferrin:neutrophil ratio became elevated, suggesting increased synthesis/release of lactoferrin from neutrophils. However, patients with myelodysplasia continued to show depressed lactoferrin:neutrophil ratios, even when there had been an increase in granulocyte count, suggesting persistent abnormalities of neutrophil lactoferrin production/release. The implications of these findings for treatment of neutropenic patients with granulocyte-macrophage colony-stimulating factors are discussed.

Topics: Adult; Anemia, Aplastic; Antineoplastic Agents; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Lactoferrin; Leukocyte Count; Male; Middle Aged; Myelodysplastic Syndromes; Neutropenia; Recombinant Proteins

The prevention of enterogenic infection by human lactoferrin was tested in five neutropenic patients receiving chemotherapy for acute myelogenous leukemia. Lactoferrin did not significantly delay the onset of infection but reduced its duration and severity as judged from the course of fever. Compared with nine matched controls, lactoferrin-treated patients had a lower incidence of bacteremia on the whole and of gram-negative bacteremia in particular.

Topics: Adolescent; Adult; Agranulocytosis; Female; Fever; Humans; Lactoferrin; Lactoglobulins; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Sepsis

A physiologic role for lactoferrin (Lf) has been implicated by (1) its antibacterial effect and (2) its involvement as a negative-feedback regulator for colony stimulating factor (CSF) and, therefore, granulocyte production. The isolation and purification of endotoxin-free, species-specific mouse and human Lf have enabled a study of the role of Lf both in vitro and in vivo. Injection of Salmonella typhimurium or LPS into mice resulted in a dose-dependent increase in plasma Lf. Treating normal and neutropenic mice with LPS showed that the plasma Lf level was directly related to the number of granulocytes found in the peripheral blood. The effect of neutropenia did not inhibit release of Lf. By incubating mouse bone marrow and adherent peritoneal cells with 0.1 microM mouse or human Lf in the absence or presence of the prostaglandin synthesis inhibitor, indomethacin (1.0 microM), no evidence could be obtained in support of a negative-feedback regulation of CSF. In fact, rather than an inhibition of CSF, the production of the latter was found to be stimulated from both cell types. Injection of endotoxin-free, mouse Lf (2 mg/animal) into mice at concentrations in the same order of magnitude as that found during bacterial infection, resulted in an increase in CSF production by 12 hours and prior to the increase in bone marrow granulocyte-macrophage progenitor cells (GM-CFC) at 48 hours. The results do not support a negative-feedback regulation of CSF by macrophages. Instead, they can be incorporated into a "demand signal" model for CSF production by macrophages.

Topics: Animals; Blood Cell Count; Bone Marrow; Cell Adhesion; Cells, Cultured; Colony-Stimulating Factors; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Growth Substances; Lactoferrin; Lactoglobulins; Lipopolysaccharides; Mice; Mice, Inbred Strains; Neutropenia; Salmonella Infections, Animal; Salmonella typhimurium; Spleen; Whole-Body Irradiation

In 20 patients with chronic neutropenia, serum lactoferrin (S-LF) and serum myeloperoxidase (S-MPO) levels were assessed. By immunofluorescence, granulocyte-bound immunoglobulins were detected in 12 patients, whereas circulating immune complexes were found in the blood of 8 patients by the 125-I-C1q-binding test (C1q-BT). In both groups of patients, there was a relative increase of S-LF and a relative or sometimes absolute increase of S-MPO. In the latter group, results of the C1q-BT correlated positively with S-MPO but negatively with neutrophil counts. No correlations between S-LF or S-MPO and the results of the granulocyte immunofluorescence test were found. Our results suggest that S-LF and S-MPO levels may be helpful in the further study of patients with chronic neutropenia, to gain more insight into the pathogenetic mechanisms operative in this disease.

Topics: Agranulocytosis; Chronic Disease; Complement Activating Enzymes; Complement C1q; Fluorescent Antibody Technique; Granulocytes; Humans; Lactoferrin; Lactoglobulins; Leukocyte Count; Neutropenia; Peroxidase

Plasma concentrations of lactoferrin were measured in immediately separated EDTA samples from 5 subjects who had received HLA identical bone marrow transplants for leukaemia or aplastic anaemia and from 7 subjects who were leukopenic as a consequence of chemotherapy for a variety of malignant conditions. Plasma lactoferrin concentrations were found to closely parallel the leucocyte count and were not found to either predict or to antedate leucocyte regeneration. Serial measurements of plasma lactoferrin in a subject with no circulating neutrophils who received a bone marrow graft revealed that the clearance of lactoferrin followed an exponential pattern and had an initial half time of 2.2 h.

Topics: Agranulocytosis; Anemia, Aplastic; Bone Marrow Transplantation; Hematopoiesis; Humans; Kinetics; Lactoferrin; Lactoglobulins; Leukemia; Leukocyte Count; Neoplasms; Neutropenia; Neutrophils

This study examines the role of plasma lactoferrin in the assessment of neutropenia. In particular, we have studied lactoferrin as an inhibitor of granulopoiesis and as an indicator of the size of the total blood granulocyte pool (TBGP). Plasma lactoferrin concentration was determined in a heterogeneous group of 30 patients with neutropenia. Serial plasma lactoferrin levels in a patient with cyclic neutropenia correlated with the cycles of the neutrophil count. Patients with splenomegaly had a grossly elevated lactoferrin:neutrophil ratio. Most chronic idiopathic neutropenia patients had no real clinical problems and a normal plasma lactoferrin level. The results provide further evidence to support the concept that plasma lactoferrin indicates the size of the TBGP and the lactoferrin: neutrophil ratio indicates the degree of granulocyte margination. There was no evidence to suggest that lactoferrin acting as a feedback inhibitor of granulopoiesis caused neutropenia in these patients.

Topics: Agranulocytosis; Anemia, Aplastic; Bone Marrow Cells; Colony-Forming Units Assay; Felty Syndrome; Humans; Lactoferrin; Lactoglobulins; Methods; Neutropenia; Radioimmunoassay

The indigenous oropharyngeal microflora is complex and consists of many different aerobic and anaerobic microorganisms. Nonindigenous pathogenic microorganisms do not normally colonize the oropharynx due to several different defense mechanisms such as cell specific bacterial attachment, secretion of antibacterial substances and immunoglobulins. Also microbial interactions play an important role in the prevention of new colonization of the oropharynx. Suppression of the indigenous flora by antibiotics promote new colonization. Patients that are severely compromised by disease may be infected by colonizing microorganisms. At special risk are patients with low neutrophil count and patients that are prone to aspiration pneumonia. Thus new colonization should be prevented in such risk patients. Careful monitoring of systemic antimicrobial therapy is essential and decontamination of oropharynx with local antimicrobial agents may be of value.

Topics: Attachment Sites, Microbiological; Bacterial Infections; Clindamycin; Erythromycin; Humans; Immune Tolerance; Lactoferrin; Lactoperoxidase; Lysosomes; Neutropenia; Oropharynx; Pneumonia, Aspiration; Risk

The functional activities of acidic isoferritins (AIF) and lactoferin (LF) were evaluated. The inhibitory activity of AIF (AIFIA) was inactivated by preincubation with a monoclonal antibody (2A4) against AIF, but AIFIA was not inactivated by another monoclonal antibody against AIF (1C5), by a monoclonal antibody (3A5) against basic isoferritins, or by a heteroantiserum (LFT) against basic isoferritins. Monoclonal 2A4 also inactivated the inhibitory activity against colony formation by granulocyte-macrophage (CFU-GM) progenitor cells that was constitutively released by human monocytes or induced by human monocytes in the presence of OKT4+ lymphocytes. In addition to OKT4+ lymphocytes, the release of AIFIA from human monocytes was modulated by iron-saturated human LF and OKT8+ lymphocytes, both of which suppressed the release of AIFIA. Evidence for the physiologic relevance of AIF as a regulator of myelopoiesis was presented, in that human AIF suppressed the numbers of CFU-GM, BFU-E, and CFU-GEMM per femur and the cycling status of these cells in mice recovering from a sublethal dosage of Cytoxan. Abnormalities in LF and AIF interactions were found with cells from a pediatric patient with neutrophilia of unknown etiology that were consistent with the disease manifestations of neutrophilia. Polymorphonuclear neutrophils (PMN) from the patient contained low levels (1%-10% of control) of immunologically reactive LF and the LF found was ineffective as a suppressor molecule for the release of GM-CSF from normal mononuclear blood cells. In addition, the patient's GM-CSF releasing mononuclear blood cells were insensitive to the suppressive effects of purified LF, and colony formation by the patient's CFU-GM, but not BFU-E or CFU-GEMM, were insensitive to the suppressive effects of purified AIF. When the activity of purified AIF was assessed against mouse bone marrow cells under serum-free conditions, it was apparent that serum was not needed for the suppressive activity of AIF and that in some cases, serum actually masked the effects of AIF. Human monoblast cell line U937 was found to be a good model in vitro for the actions of LF and AIF; U937 cells induced for Ia-antigens by human gamma interferon were separated into populations of Ia-antigen+ and Ia-antigen- cells by fluorescence activated cell sorting (FACS), and LF and AIF suppressed colony formation only by the Ia-antigen+ U937 cells. A comparative analysis of bovine and human LF against release of GM-CSF fr

Topics: Animals; Antibodies, Monoclonal; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Child; Colony-Forming Units Assay; Female; Ferritins; Granulocytes; Hematopoietic Stem Cells; Humans; Hydrogen-Ion Concentration; Lactoferrin; Lactoglobulins; Macrophages; Mice; Milk, Human; Neutropenia; Pregnancy; Reference Values

Topics: Cellulose; Complement Activation; Humans; Lactoferrin; Membranes, Artificial; Neutropenia; Neutrophils; Prospective Studies; Renal Dialysis

Plasmatic lactoferrin measure (LF) by immuno-enzymatic technique combined with neutrophil blood count (PN) on 100 subjects (controls and patients) allows us to show a LF increase proportional to circulating blood neutrophils. In neutropenia, plasmatic lactoferrin measure seems able to divide the central causes from the peripheric ones. Regarding the granulocytosis, LF levels are clearly higher in myeloproliferative diseases than in other causes. Lactoferrin could therefore represent an index of total circulating neutrophil pool but also seems to reflect the granulocyte activation.

Topics: Adult; Female; Humans; Lactoferrin; Lactoglobulins; Leukocyte Count; Leukocytosis; Male; Neutropenia; Neutrophils

Rabbit granulocyte lactoferrin, when infused into hamsters or rabbits, induces transient neutropenia, and in hamsters the lactoferrin promotes adherence of the granulocytes to the endothelial cell wall as monitored visually. In contrast, neither rabbit granule lysozyme nor human transferrin induces neutropenia in the rabbit nor does transferrin or bovine serum albumin affect the adherent properties in vivo of the phagocytic cells of the hamster. Thus lactoferrin enhances granulocyte adherence both in vivo and in vitro. It would appear that the promotion of margination of leukocytes by lactoferrin in vivo may contribute to the phenomenon of neutropenia during activation of granulocytes by chemotactic factors.

Topics: Agranulocytosis; Albumins; Animals; Cell Adhesion; Cell Aggregation; Chemotactic Factors; Cricetinae; Endothelium; Granulocytes; Infusions, Parenteral; Lactoferrin; Lactoglobulins; Leukocyte Count; Muramidase; Neutropenia; Rabbits; Transferrin

Radioimmunosorbent assays for determination of serum content of the neutrophil proteins myeloperoxidase and lactoferrin are described. Serial studies were performed in patients with neutropenia. In 2 cases of cyclic neutropenia the myeloperoxidase level showed slight variations within the normal range during the cycle while lactoferrin displayed a clear correlation with neutrophil counts. In 1 case with persistent agranulocytosis myeloperoxidase was normal but lactoferrin was extremely low. During the regeneration phase of drug-induced neutropenia neutrophil counts and serum lactoferrin increased in a parallel fashion. Since serum myeloperoxidase was normal during profounded neutropenia it is suggested to derive primarily from myeloperoxidase-rich granulopoietic precursor cells of the marrow. Serum lactoferrin on the other hand seems to derive from leakage of more granulopoietic cells of blood and marrow. Studies of neutrophil proteins of serum may aid in evaluation of neutropenic patients.

Topics: Adolescent; Adult; Agranulocytosis; Female; Humans; Lactoferrin; Lactoglobulins; Leukocyte Count; Male; Neutropenia; Periodicity; Peroxidase; Peroxidases; Radioimmunosorbent Test