Activation of human inflammatory cells by secreted phospholipases A2.
Secreted phospholipases A(2) (sPLA(2)s) are enzymes detected in serum and biological fluids of patients with various inflammatory, autoimmune and allergic disorders. Different isoforms of sPLA(2)s are expressed and released by human inflammatory cells, such as neutrophils, eosinophils, T cells, monocytes, macrophages and mast cells. sPLA(2)s generate arachidonic acid and lysophospholipids thus contributing to the production of bioactive lipid mediators in inflammatory cells. However, sPLA(2)s also activate human inflammatory cells by mechanisms unrelated to their enzymatic activity. Several human and non-human sPLA(2)s induce degranulation of mast cells, neutrophils and eosinophils and activate exocytosis in macrophages. In addition some, but not all, sPLA(2) isoforms promote cytokine and chemokine production from macrophages, neutrophils, eosinophils, monocytes and endothelial cells. These effects are primarily mediated by binding of sPLA(2)s to specific membrane targets (heparan sulfate proteoglycans, M-type, N-type or mannose receptors) expressed on effector cells. Thus, sPLA(2)s may play an important role in the initiation and amplification of inflammatory reactions by at least two mechanisms: production of lipid mediators and direct activation of inflammatory cells. Selective inhibitors of sPLA(2)-enzymatic activity and specific antagonists of sPLA(2) receptors are current being tested for pharmacological treatment of inflammatory and autoimmune diseases.
Triggiani
Massimo
M
Division of Clinical Immunology and Allergy, Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80131 Naples, Via Pansini 5, Italy. triggian@unina.it
Granata
Francescopaolo
F
Frattini
Annunziata
A
Marone
Gianni
G
D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D005089:Exocytosis / Q000276:immunology; D006497:Heparan Sulfate / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D010741:Phospholipases A / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011509:Proteoglycans / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism
D006497:Heparan Sulfate; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D010741:Phospholipases A; D011509:Proteoglycans; D011956:Receptors, Cell Surface