Fibrin enhances the expression of IL-1 beta by human peripheral blood mononuclear cells. Implications in pulmonary inflammation.
Tissue injury is accompanied by increased vascular permeability and influx of plasma proteins including fibrinogen. Fibrinogen is converted into a fibrin matrix by procoagulants activated at the site of tissue injury and inflammation. This fibrin matrix is thought to participate early in the inflammatory response by providing a temporary protein "scaffold" for inflammatory cell adhesion and migration, and subsequent remodeling of the tissue with permanent extracellular matrix proteins such as collagen. Collagen and fibronectin have been shown to regulate the expression of inflammatory cytokines, but whether fibrin can regulate cytokine expression is not known. We hypothesized that fibrin induces the expression of the proinflammatory cytokine IL-1 beta and sought to explore mechanisms responsible for this induction. In this report, we demonstrate that fibrin stimulates human PBMCs to express IL-1 beta message and protein. We show that induction of IL-1 beta by fibrin is mediated partly by the integrin receptor CD11b/CD18 and modulated by cytoskeletal rearrangement. Fibrin also suppresses production of IL-1 receptor antagonist (IL-1ra) a non-bioactive competitor of IL-1 for IL-1Rs. We propose that injured tissues where the conditions favor coagulation and fibrin accumulation, the interaction between mononuclear cells and the newly formed fibrin matrices may elicit the production of the proinflammatory cytokine IL-1 beta. This proposal is supported by immunohistochemical studies which show the co-distribution of fibrin and IL-1 beta in granulomas in lung sections from patients with the systemic granulomatous disease, sarcoidosis.
Department of Medicine, Atlanta Veterans Affairs Medical Center, Emory University School of Medicine, GA 30033.
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Perez
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Roman
D018821:CD18 Antigens / Q000502:physiology; D002199:Capillary Permeability; D003599:Cytoskeleton / Q000648:ultrastructure; D005337:Fibrin / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006099:Granuloma / Q000473:pathology; D006801:Humans; D007249:Inflammation; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D017565:Sarcoidosis, Pulmonary / Q000473:pathology; D012795:Sialoglycoproteins / Q000096:biosynthesis
D018821:CD18 Antigens; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D005337:Fibrin; D005340:Fibrinogen