Activation Of Integrin LFA-1 Under Flows

In the circulation of blood flow,vascular endothelial cells participate in many other biological processes as regulation of leukocytes,platelet adhesion,inflammation and atherosclerosis.Leukocyte adhesion is important in physiological and pathological process,especially in the inflammatory,which is a complex,multistep process of cascade need combination of many factors.The current study found that endothelial cells secrete inflammatory mediators such as chemokines and immunoglobulin molecules play an important role in leukocyte adhesion.Chemokines are significant in leukocyte migration,which mediate migration of leukocyte from blood into tissue through regulating the leukocyte motility,so that it can raise defense cell to the site of inflammation.Integrin played a decisive role in leukocyte stability adhesion to the endothelial cells surface.As the main ligand of integrin LFA-1,ICAM-1 can be expressed in a variety of cells,and it often act as dimers.After the activation of chemotactic factor CXCL12,LFA–1 affinity state transited from low to high so that it can interaction of ICAM-1.Only under blood shear stress,it can open followed activation process completely by Outside-in signal pathway.The combination of LFA-1 and ICAM-1 depends on their combining ability which is dynamic,and it is regulated by the affinity of LFA-1.This study used Jurkat cells,CXCL12 and LFA-1 as experimental object,parallel plate flow chamber as experiment means,combining theoretical modeling and experimental observation,observed interaction LFA-1 and ICAM-1 in vitro.We study its two-dimensional reaction kinetics,activation level,the activation rate and inactivation rate,etc.,so as to reveal regulation of force and CXCL12.This study deepening the understand of the leukocyte in the inflammatory immune response,thrombosis and tumor metastasis,which is currently one of the hot topics in the study of life.