cathepsin-g and Infections

The migration of leukocytes such as neutrophils, monocytes and lymphocytes into inflamed lesions is one of the critical events of inflammation. Although the traditional function of neutrophil-derived antimicrobial proteases is to ingest and kill bacteria, some neutrophil serine proteases have been shown to induce leukocyte migration and activation. Mast cell-derived chymase also has the chemotactic activity for leukocytes. During the acute phase of inflammatory and allergic diseases, the predominantly migrated cells are neutrophils and mast cells, respectively, and in the subsequent chronic phase, monocytes and lymphocytes are mainly migrated. The chemotactic activity for monocytes and lymphocytes of neutrophil-derived serine proteases and mast cell-derived chymase may have a role in switching acute inflammation to chronic inflammation and delayed-type hypersensitivity. Recently, aminopeptidase N and endothelin were shown to induce chemotactic migration of leukocytes. Thus, protease-induced leukocyte chemotaxis and activation may play an important role in immunologic events of inflammatory and allergic diseases.

Topics: Antimicrobial Cationic Peptides; Blood Proteins; Carrier Proteins; Cathepsin G; Cathepsins; CD13 Antigens; Chemotaxis, Leukocyte; Chymases; Endopeptidases; Endothelins; Endothelium, Vascular; Hypersensitivity, Delayed; Infections; Inflammation; Lymphocyte Activation; Mast Cells; Monocytes; Neoplasms; Neutrophils; Sarcoidosis; Serine Endopeptidases; T-Lymphocyte Subsets

Atypical antineutrophil cytoplasm antibodies (A-ANCA) are defined here as ANCA detected by IIF and not directed against the predominant ANCA antigens, proteinase 3 (PR3) and myeloperoxidase (MPO). A-ANCA are found in a variety of clinical conditions, namely rheumatoid arthritis, inflammatory bowel diseases, chronic hepatic diseases and several infections including HIV infection. They are directed against a variety of still ill-defined neutrophil antigens and most frequently yield a perinuclear pattern (P-ANCA) of binding by indirect immunofluorescence on ethanol fixed neutrophils. This paper reviews the literature on A-ANCA and our recent data suggesting that, among others, cathepsin G is one of the predominant antigen targets of A-ANCA. From a clinical point of view, the distinction between MPO-ANCA and A-ANCA is not possible by indirect immunofluorescence (IIF). The determination of ANCA antigens by specific ELISA is therefore necessary to differentiate P-ANCA with MPO specificity from those with undefined specificity. This is of importance because the clinical value of MPO-ANCA is clearly established while the presence of A-ANCA is difficult to interpret given their occurrence in a large variety of clinical conditions.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Autoimmune Diseases; Cathepsin G; Cathepsins; Cytoplasm; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Humans; Infections; Inflammatory Bowel Diseases; Liver Diseases; Myeloblastin; Neutrophils; Pancreatic Elastase; Peroxidase; Serine Endopeptidases