Journal of - Nobel Medical College

Kafle Dillioperate, in part, by increasing the reactivityof platelets. 6Fibrinogen and inflammation:The process of inflammation is primarilymediated by its interaction with leucocytesthrough the surface receptors of the lattertermed ‘integrins. The 2 main receptors forfibrinogen on the surface of leukocytesinclude Mac-1 (CD11b/CD beta 2) andalpha X beta 2 (CD11c/CD18,). Leukocytes(both monocytes and myelocytes) canspecifically induce MAC–1 receptor to bindfibrinogen. 7,8 The ability of MAC–1 receptorto bind fibrinogen results from thematurational changes occurring in thereceptor during the process of celldifferentiation, and is not seen in aresting leukocyte. The site on fibrinogenthat interacts with MAC-1 is not shared byother integrins. 9Fibrinogen is also a ligand for IntercellularAdhesion Molecule-1 (ICAM-1), andenhances monocyte-endothelial cellinteraction by bridging the Mac-1 onmonocytes to ICAM-1 on endothelialcells. 10,11 Thus ICAM-1 behaves as a cellsurface ligand for alpha beta 2 and alphaM beta 2 (MAC-1) integrins, and has akey role in leukocyte adhesion to thevascular endothelium. Furthermore,fibrinogen up regulates and increasesthe concentration of ICAM-1 proteins onthe surface of endothelial cells, resultingin increased adhesion of leukocytes on thesurface of endothelial cells 12 , even at highshear rates in flow conditions. 13 Moreover,the fibrinogen binding to ICAM-1 on theendothelial cells also mediates the adhesionof platelets. The interaction of fibrinogenand cells expressing ICAM-1 is associatedwith cellular proliferation. 14Fibrinogen, on binding to its integrinreceptor on the surface of leukocytesalso facilitates a chemotactic response, thusplaying a vital role in the process ofinflammation. 15 One of the proposedmechanisms by which fibrinogen inducesproinflammatory changes in leukocytesincludes an increase in the free intracellularcalcium and increased expression ofneutrophil activation markers Theseprocesses result in an increase inphagocytosis,antibody-mediatedleucocyte toxicity and delay inapoptosis. 16Fibrinogen is also involved in thefacilitation of both cell–cell interaction andthe interaction of cell and extracellularmatrix such as collagen. 7,17 Thus, asexplained above, fibrinogen is an importantmediator of cell–cell interaction, adhesionand inflammation.Finally, there is evidence that fibrinogenfacilitates the biomaterial-provokedinflammatory response. 18 Interaction withthe biomaterial results in conformationalchanges within the fibrinogen moleculeand conversion into ‘proinflammatory’fibrinogen, resulting in the exposure of theepitope that interacts with the MAC-1receptor for macrophages. 18,19Fibrinogen and atherogenesis:There seems to be little doubt thatfibrin deposition can both initiateatherogenesis and contribute to the growthof plaques. 46,47 Fibrinogen and itsmetabolites appear to cause endothelialdamage and dysfunction by a number ofmechanisms. 48 Many human atheroscleroticlesions, showing no evidence of fissure orulceration, can contain a large amount offibrin, which may either be in the form ofmural thrombus on the intact surface of theplaque, in layers within the fibrous cap, inthe lipid-rich core, or diffusely distributedthroughout the plaque. This phenomenonJournal of Nobel Medical College (2011), Vol. N.1 2