lactoferrin and Immunologic-Deficiency-Syndromes

Topics: Animals; CCAAT-Enhancer-Binding Proteins; Cytoplasmic Granules; Diagnosis, Differential; Frameshift Mutation; Humans; Immunologic Deficiency Syndromes; Infections; Lactoferrin; Neutrophils; Prognosis; Recurrence

Phagocytosis begins with exocytosis--"extrarapid" discharge of bactericidal proteins and factors of permeability into the extracellular medium. A viewpoint was put forward on an "avalanch-like" character of the outcome of cationic proteins from leukocyte granules in inflammation and their participation in formation of a nonphagocytic type of resistance. In phagocytosis bacteria perish due to the myeloperoxidase system, lysozyme, lactoferin and nonenzymic cationic proteins. Hereditary deficit of the above-mentioned substances leads to intraleukocytic microbicidal insufficiency, a drastic decrease in the nonspecific resistance of the organism and to development of fatal granulomatous disease, and to other forms of pathology associated with genetic defects of the bactericidal systems of leukocytes.

Topics: Blood Bactericidal Activity; Blood Proteins; Cell Membrane Permeability; Cytoplasmic Granules; Exocytosis; Glucosephosphate Dehydrogenase Deficiency; Histones; Humans; Immunity; Immunologic Deficiency Syndromes; Inflammation; Lactoferrin; Microscopy, Phase-Contrast; Muramidase; Neutrophils; Peroxidase; Phagocytosis

Topics: Agammaglobulinemia; Anemia, Sickle Cell; Chemotaxis; Female; Glucosephosphate Dehydrogenase Deficiency; Humans; Immunity, Cellular; Immunoglobulin E; Immunologic Deficiency Syndromes; Infections; Job Syndrome; Lactoferrin; Leukocytes; Male; Muramidase; Opsonin Proteins; Peroxidase; Phagocytes; Phagocytosis; Staphylococcus

Topics: CCAAT-Enhancer-Binding Proteins; Chromosomal Proteins, Non-Histone; Homozygote; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Lactoferrin; Leukocyte Disorders; Male; Neutrophils

Chemotherapy is one of the main treatments for cancer; however, it usually causes severe atrophy of immune organs and self-immunity damage to patients. Human lactoferrin (hLF) is a multiple biofunctional protein in regulating the immune response and thus holds great promise to alleviate chemotherapy-caused immunosuppression. However, a sufficient hLF resource and efficient delivery of hLF remain a challenge. Here, we provide a useful strategy to simultaneously solve these two problems. A silk sericin hydrogel system delivering recombinant hLF (SSH-rhLF) was fabricated to alleviate the chemotherapeutic drug-caused side effects by rhLF-carrying silk cocoons, which were cost-effectively produced by a transgenic silkworm strain as the resource. SSH-rhLF with a uniform porous microstructural morphology, a dominant β-sheet internal structure, adjustable concentration and sustainable release of the rhLF, and non-cytotoxicity properties was demonstrated. Interestingly, the sericin hydrogel showed effective protection of the rhLF from degradation in the stomach and small intestine, thus prolonging the bioactivity and bioavailability of rhLF. As a result, the oral administration of SSH-rhLF with a low rhLF dose showed significant therapeutic effects on enhancing the immune organs of cyclophosphamide (CTX)-treated mice by protecting the splenic follicles, promoting the expression of immunoregulatory factors, and recovering the intestinal flora family from CTX-induced imbalance, which were similar to those achieved by oral administration of a high dose of free hLF in the solution form. The results suggest that the strategy of producing rhLF silk cocoons via feeding transgenic silkworms overcomes well the shortage of rhLF resources, improves the bioavailability of oral rhLF, and alleviates the side effects of chemotherapeutic drugs on immune organs. The oral SSH-rhLF will be promising for applications in cancer chemotherapy and immunity enhancement of patients.

Topics: Administration, Oral; Animals; Animals, Genetically Modified; Bombyx; Cyclophosphamide; Drug Carriers; Drug Stability; Female; Gastrointestinal Microbiome; Humans; Hydrogels; Immunologic Deficiency Syndromes; Lactoferrin; Mice, Inbred BALB C; Recombinant Proteins; Sericins

Neutrophil-specific granule deficiency (SGD) is a rare, congenital disorder characterized by atypical neutrophil structure and function that results in frequent and severe bacterial infections. However, the clinical course of patients with SGD have not been described in detail because of the scarcity of the disease. We present the clinical course of an adult patient with SGD and propose a method for making an early diagnosis of SGD.. A32-year-old Japanese woman with SGD had a small impetigo lesion on her face and experienced the rapid spread of a facial abscess to a pulmonary abscess via the blood stream. We also analyzed the expression of neutrophil granule proteins in our patient compared with a healthy control by flow cytometry.. We confirmed defects of several neutrophil granule proteins in our patient by flow cytometry.. Severe bacterial infections sometimes occur and spread rapidly in SGD. Detection of neutrophil granules by flow cytometry is useful for a rapid diagnosis and a screening of SGD.

Topics: Acute-Phase Proteins; Adult; Antibiotic Prophylaxis; Antimicrobial Cationic Peptides; Blood Proteins; Cathelicidins; CCAAT-Enhancer-Binding Proteins; Debridement; Defensins; Female; Flow Cytometry; Humans; Immunologic Deficiency Syndromes; Impetigo; Japan; Lactoferrin; Lipocalin-2; Lipocalins; Lung Abscess; Mutation; Neutrophils; Peroxidase; Proto-Oncogene Proteins; Secretory Vesicles

Previous studies on neutrophils in patients with the myelodysplastic syndromes (MDS) have indicated deficiencies in the contents of primary and secondary granules. However, the granule membrane remains virtually unstudied despite its essential role in the dynamic function of the cytoplasmic granules. In this study, we examined the membrane glycoproteins of primary and secondary granules of peripheral blood and/or bone marrow neutrophils using the monoclonal antibody H36/71 to CD15 glycoproteins. In addition, myeloperoxidase activity and antigen, elastase and lactoferrin were also studied using cytochemical and immunocytochemical stains. A total of 216 patients were included. Deficiencies of granule membrane glycoproteins were the most common, detected in 49%, followed by myeloperoxidase activity (17%), elastase (16%), myeloperoxidase antigen (9%), and lactoferrin (8%). Multiple deficiencies always included granule membrane deficiency. We conclude that granule membrane defects are common in MDS, may provide a common mechanism for multiple granule deficiencies, and may prove to be an additional abnormality associated with granulocyte dysfunction.

Topics: Cytoplasmic Granules; Humans; Immunologic Deficiency Syndromes; Intracellular Membranes; Lactoferrin; Leukocyte Elastase; Lewis X Antigen; Membrane Glycoproteins; Myelodysplastic Syndromes; Neutrophils; Peroxidase

Skin test anergy, the failure to produce a delayed type hypersensitivity (DTH) response, is associated with an increase in infection-related complications and death usually due to multiple organ failure (MOF). Refractory intravascular activation of polymorphonuclear neutrophils (PMNs) has been implicated in the development of MOF. We studied 20 critically ill surgical patients with life threatening infections to determine if PMN intravascular activation was present and how this affected essential PMN functions such as exudation. The 11 anergic patients had a more intense inflammatory response to their infection. Plasma lactoferrin was 6.1 +/- 0.3 microgram/ml in anergic patients compared to 3.9 +/- 1.5 in reactive P less than 0.05, accompanied by reduced total primary (3.3 +/- 1.9 vs 4.7 +/- 2.1 micrograms/10(6) PMN P less than 0.01) and secondary (2.8 +/- 0.4 vs 5.0 +/- 0.9 microgram/10(6) PMN P less than 0.01) granule content, respectively. In vitro superoxide production following 100 ng/ml PMA stimulation was 0.44 +/- 0.1 in anergics vs 0.36 +/- 0.1 nmol/microgram PMN protein in reactivities, P less than 0.05. PMN chemotaxis was 8.2 +/- 0.6 PMNs/HPF in anergics compared to 10.2 +/- 1.6 PMNs/HPF in reactives P less than 0.05, accompanied by decreased PMN delivery to skin blister windows (3.2 +/- 1.4 vs 4.5 +/- 1.9 x 10(7) PMN/ml, respectively, P less than 0.05). We conclude that critically ill anergic surgical patients have increased intravascular PMN activation, which may contribute to oxygen-derived tissue damage in the vascular space, as well as a deficient delivery of effector cells in areas of bacterial invasion. This may lead to inability to clear the inflammatory signals which set up the vicious circle of MOF leading to death.

Topics: Cell Adhesion; Cell Degranulation; Chemotaxis, Leukocyte; Exudates and Transudates; Glucuronidase; Humans; Hypersensitivity, Delayed; Immunologic Deficiency Syndromes; Inflammation; Lactoferrin; Macrophage-1 Antigen; Neutrophils; Respiratory Burst; Skin Tests; Superoxides; Surgical Procedures, Operative

Most infections reach man via the mucosal membranes, and more than half of the lymphoid system is found in connection with mucosae. The major antibodies found on mucous membranes are secretory IgA, which function primarily by binding microorganisms and thereby preventing their contact with the host tissues. The optimal mode of immunization to obtain a secretory IgA response is not well defined. Repeated mucosal exposure with antigen may result in oral tolerance, with decreasing circulating antibodies but a remaining secretory IgA response. The secretory IgA response is usually short-lived and can be difficult to boost. IgM as well as IgG antibodies may add to host defence at the mucosal level, but when engaged, they usually induce inflammation in host tissues. Analogues to bacterial receptors on mucosal epithelium may be present in exocrine secretions such as human milk. During an attack on the host, it is possible that such receptor analogues may aid in the prevention of attachment of bacteria to mucous membranes used as an initial site. A number of non-specific host factors support mucosal defence. One of them is lactoferrin. Lactoferrin deficiency seems to result in recurrent bacterial infections, suggesting its importance in normal host defence.

Topics: Antibody Formation; Antigens, Bacterial; Bacterial Infections; Epithelium; Humans; Immunity, Cellular; Immunoglobulin A, Secretory; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Lactoferrin; Mucous Membrane; Receptors, Immunologic; Secretory Component