Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Abstract

Coagulation is fundamental for the confinement of infection and/or the inflammatory response to a limited area. Under pathological inflammatory conditions such as arthritis, multiple sclerosis or sepsis, an uncontrolled activation of the coagulation system contributes to inflammation, microvascular failure and organ dysfunction. Coagulation is initiated by the activation of thrombin, which, in turn, triggers fibrin formation by the release of fibrinopeptides. Fibrin is cleaved by plasmin, resulting in clot lysis and an accompanied generation of fibrin fragments such as D and E fragments. Various coagulation factors, including fibrinogen and/or fibrin [fibrin(ogen)] and also fibrin degradation products, modulate the inflammatory response by affecting leukocyte migration and cytokine production. Fibrin fragments are mostly proinflammatory, however, Bβ15-42 in particular possesses potential antiinflammatory effects. Bβ15-42 inhibits Rho-kinase activation by dissociating Fyn from Rho and, hence prevents stress-induced loss of endothelial barrier function and also leukocyte migration. This article summarizes the state-of-the-art in inflammatory modulation by fibrin(ogen) and fibrin fragments. However, further research is required to gain better understanding of the entire role fibrin fragments play during inflammation and, possibly, disease development.

Increased Oxidant Stress and Inflammation in Patients with Chronic Schizophrenia

“…In the previous studies, it was shown that neither individual antioxidant levels nor total antioxidant status were significantly affected by antipsychotic treatment [25,[50][51][52]. More importantly, the altered antioxidants observed were independent of treatment since patients were antipsychotic drug-naive at entry into the study [29,50,51].…”

“…Fibrin (ogen) has been shown to cause an inflammatory response in peripheral blood mononuclear cells induced by high levels of reactive oxygen species, increased cytokine and chemokine expression and macrophage chemoattractant protein-1 [25]. In their review, Leonard et al stated that inflammatory mediators including CRP and fibrinogen, are raised in the serum of patients with schizophrenia.…”

Discrepant coagulation profile in HIV infection

“…In future studies, supplementary biomarkers of coagulation, that is thrombin or split products of fibrin(ogen), may be of interest to determine whether elevated D-dimer reflects increased clot formation or fibrinolysis [34].…”

Thrombin and plasmin-like activities in the latices of Cryptostegia grandiflora and Plumeria rubra

“…The inflammatory process is closely associated with activation of the coagulation cascade. A variety of inflammatory diseases such as sepsis, rheumatoid arthritis and multiple sclerosis not only has its effects attributed to an uncontrolled inflammatory response, but also to a disturbance of coagulation [18]. Thus, when coagulation is impaired, it can contribute to the pathogenesis of many inflammatory diseases through fibrin deposition and microvascular insufficiency, as well as by enhancing the inflammatory response [33].…”

“…This is a natural response of the body to injury [17]. Fibrinolysis dissolves fibrin clot through the action of plasmin, facilitating wound healing and restoring the normal flow of blood [18].…”