Molecular regulators of leucocyte chemotaxis during inflammation.
A fundamental feature of any immune response is the movement of leucocytes from one site in the body to another to provide effector functions. Therefore, elucidating the molecular mechanisms underlying the migration of leucocytes from the blood to tissues is critical to our understanding of immune function during inflammation. The classic steps of leucocyte trafficking involve leucocyte tethering and rolling on vessel walls of the vasculature, followed by firm adhesion to the endothelium. Recent evidence suggests that upon adhering, leucocytes crawl within the vessels before transmigrating across vessel walls and crawling into targeted tissues. The directed nature of the crawling events is orchestrated by a complex array of soluble factors and molecular regulators in combination with the local intravascular and extracellular environment. In fact, this process is known as chemotaxis and orientates cell movement in relation to the ligand gradient. Several signalling pathways have been proposed to be involved in this gradient-sensing and amplification process, but the best studied, discussed in detail here, is the phosphatidylinositol 3-kinase pathway. Substantial progress has been made in understanding how cells roll and adhere in blood vessels; however, how cells crawl in blood vessels, emigrate, and then crawl in tissues has received much less attention. Therefore, the focus of this review is to provide recent insights into molecular mechanisms and cellular processes that mediate leucocyte crawling in blood vessels and tissues during the inflammatory response.
Wong
Connie H Y
CH
Department of Physiology and Biophysics, Calvin, Phoebe and Joan Snyder Institute for Infection, Immunity and Inflammation, University of Calgary, HRIC 4A26A, 3280 Hospital Drive NW, Alberta, Canada T2N 4N1. chwong@ucalgary.ca
Heit
Bryan
B
Kubes
Paul
P
D000818:Animals; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D016023:Integrins / Q000276:immunology; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D015398:Signal Transduction
D018836:Inflammation Mediators; D016023:Integrins; D019869:Phosphatidylinositol 3-Kinases