Role And Mechanism Of Lipid Raft And Lipid Raft-associated ?-adducin In ?2 Integrin-Mediated Neutrophil Migration

Neutrophils is the biggest class group of the peripheral blood in human body,they undertake important responsibilities in the early inflammatory response,and cell migration is the premise of neutrophils' physiological function.When bacteria and other pathogens are attacking the body,neutrophils are the first class group to be recruited to the infection site among all of the leukocytes,which acts as the first line of defense to resist external stimulate in the orgnism,and the establishment of this kind of defense mechanism is based on the migration of neutrophils and chemokines.But as a result of the large-scale infiltration of neutrophils to the organization in the pathological conditions can cause excessive inflammation,which often leads to serious irreversible damage to the body,such as acute respiratory distress syndrome and acute lung injury and related inflammatory disease.So deeply investigate the molecular mechanism of neutrophil migration process migration of neutrophils,analyze the interference effect of molecular targets,will has very important physiological and pathological significance.Lipid rafts are the micro-structures in cell membrane which are rich of phospholipids and cholesterol,it can enrich a large amounts of protein and lipid molecules,helps enhance the interactions of molecules in lipid rafts,which makes the lipid rafts play a crucial role in the processes fo the cell polarization,adhesion,migration,cell signal transduction,protein transportation.Lipid rafts related proteins play an impotant role in the process of raising perfected lipid raft structure model.The cell cortex skeleton proteins are the notable regulators in numerous lipid rafts related proteins,cell cortical skeleton is the component of cytoskeleton,they are a bridge of the plasma membrane and cytoskeleton which are positioning under the plasma membrane.?-adducin is a member of the membrane skeleton proteins family,it is the exclusive connection of cell membrane and cytoskeleton.Laboratory prophase work indicates that ?-adducin plays an important role in the process of leukocyte rolling.In the process of neutrophils migration,the cell membrane keeping stretching out of filamentous and flake pseudopodia also need the membrane constantly separate from the cytoskeleton,need the cluster activities of cytoskeleton under the cell membrane to promote cell movement process.So we suggested that the lipid rafts-relatd membrane skeleton protein ?-adducin may play a certain role in mediating neutrophils migration also.This article will mainly discuss the role and function of the lipid rafts and the ?-adducin in neutrophil migration process.In this paper,we use the Tranwell migration model to discuss the lipid rafts' function in ?2 integrin mediated neutrophil migration process,we used the living cells microscopic imaging analysis system to observe the influence of the integrated lipid rafts in the migration of neutrophils.Analyse and research the role and mechanism of lipid raft-associated ?-adducin in ?2 integrin-mediated neutrophil migration by some experimental methods and technologies,such as immunofluorescence labeling,confocal microscopy,virus infection,immune precipitation,western blot,sucrose density gradient centrifugation.In our reasearch,we find out that lipid raft-associated ?-adducin plays an important role in ?2 integrin-mediated neutrophil migration.When the lipid rafts structural integrity are damaged,no matter neutrophils organization process of infiltration or migration behavior are significantly affected.We deleted a section of endogenous ?-adducin by virus infection and found that ?2 integrin-mediated neutrophil migration process severely inhibition.Using sucrose density gradient centrifugation separation of lipid rafts composition,immunofluorescence double labeling methods,we found that the ?-adducin have a reposition when we use the chemokines fMLP to stimulate the neutrophils.?-adducin and lipid raft structures' co-positioning is regulated by the phosphorylation of tyrosine residues on the end of ?-adducin.Our study reveals the the function and mechanism fo the lipid rafts and its related proteins in ?2 integrin-mediated neutrophil migration process.Deeply explain the molecular mechanism of migration of neutrophils,and find the interference neutrophil migration molecular targets of blocking excessive inflammatory reaction caused by the neutrophils large-scale infiltration in pathological conditions,it has an important significance.