Cross talk between the inflammation and coagulation systems.

1. J Lynne Williams[⇑][1] 1. is professor and program director, Medical Laboratory Sciences, Oakland University, Rochester MI 1. Address for correspondence: J Lynne Williams PhD CLS(NCA), professor and program director, Medical Laboratory Sciences, Oakland University, Rochester MI 48309. (248) 370-4040, (248) 370-4227 (fax).jlwillia{at}oakland.edu. 1. Identify the major components (cellular and inflammatory mediators) of inflammation. 2. Describe the functions of the inflammatory response. 3. List the major inflammatory cytokines. 4. Identify the significant effects of the inflammatory mediators on the coagulation and fibrinolytic systems. 5. Identify the significant effects of the coagulation and fibrinolytic systems on inflammation. Previously, blood coagulation and inflammation were thought to be completely different physiologic processes. It is now recognized, however, that these two systems are interrelated as part of the host defense mechanism.1,2 In invertebrates, the functions of clotting and inflammation are mediated by a single cell system, the hemocyte.3 In vertebrates, clotting and inflammation have diverged into the specialized functions of the platelets, phagocytic cells (neutrophils and macrophages), and several plasma protein systems (procoagulant proteins, complement proteins, proteins of the kinin system). Several observations suggest an ongoing interaction between these two systems. There is significant structural homology between the proteins of the complement and coagulation cascades. Both cascades utilize serine proteases and are activated through a series of proteolytic cleavage reactions. Animals subjected to experimental sepsis have multi-organ failure associated with activation of blood coagulation (mediated primarily by inflammatory mechanisms). Inhibition of coagulation factor Xa activity inhibits fibrin formation but does not reduce mortality in this model system. However, inhibition of tissue factor/factor VIIa activity or infusion of activated protein C not only reduces fibrin formation, but also significantly reduces mortality.4 Thus, there are interactions between the proteins of these two systems that go beyond simply the activation of fibrin formation. Both coagulation and inflammation are essential parts of the host defensive response. These pathways have several connecting points through which they interact. Importantly, the interaction between coagulation and inflammation is bidirectional: both inflammation-induced coagulation as well as coagulation-induced inflammation occur.5 THE INFLAMMATORY RESPONSE The inflammatory response refers to the biochemical… ABBREVATIONS: APC = activated protein C; AT = antithrombin; C4bBP = C4b binding protein; DIC = disseminated intravascular coagulation; EC = endothelial cells; EPCR = endothelial cell protein C receptor; GAG = glycosaminoglycans; PAF = platelet activating factor; PAI-1 = plasminogen activator inhibitor-1; PARs= protease activated receptor; PC = protein C; PDGF = platelet derived growth factor; TAFI = thrombin activated fibrinolysis inhibitor; TFPI = tissue factor pathway inhibitor; TM = thrombomodulin; TNF = tumor necrosis factor; ULVWF = ultra-large multimers of von Willebrand factor. 1. Identify the major components (cellular and inflammatory mediators) of inflammation. 2. Describe the functions of the inflammatory response. 3. List the major inflammatory cytokines. 4. Identify the significant effects of the inflammatory mediators on the coagulation and fibrinolytic systems. 5. Identify the significant effects of the coagulation and fibrinolytic systems on inflammation. [1]: #corresp-1