Calcium Response Of Jurkat T Cells Mediated By Chemokine CXCL12 And Integrin LFA-1 Under Flow

As important immune cells,lymphocytes play a key role in resisting antigen invasion.Due to its presence in the blood flow environment,it is required for lymphocytes to adhere to blood vesssels near inflammation sites first to realize their immune function,preparing for the gradual migration across vascular barrier to the inflammatory tissue.This is an extremely complex multi-step cascade reaction process involving the combined action of multiple biological factors and physical factors.Current studies suggest that chemokines and immunoglobulin molecules(selectin),expressed in the internal surface of blood vessels near the site of inflammation,play important roles in the process of lymphocytes adhesion.It is generally believed that selectin mediates the rapid rolling of lymphocytes on endothelial cells,while chemokine plays the role of activating integrins which mediate the slow rolling and firm adhesion of cells.The activation of integrin is a key step in this process and calcium response has been thought to occur before integrin activation.Calcium response is one of the markers of activation of non-excitatory cells and is an important means to study integrin activation signal.In this study calcium response was used as a method.Jurkat T cells,chemokine CXCL12 and integrin LFA-1 were chosen as research objects.The parallel plate flow chamber was selected to simulate true conditions of human blood.Delay time,activation ratio and some other parameters were extracted to investigate the effects of fluid shear stress and extracellular calcium ions on the calcium response imdiated by CXCL12 in a still or a flow situation,with or without extracellular calcium ions,and to investigate the sequence of integrin LFA-1 activation and cellular calcium response.The results shown that fluid shear stress initiated the calcium response in Jurkat T cells induced by immobilized CXCL12 and extracellular calcium ions influx preceded calcium response.The influx of calcium ions accelerated the process of calcium response.Activation of integrin LFA-1 induced by CXCL12 occurred befored calcium response.This study provides a new mechanochemical coupling regulation mechanism for physiological and pathological processes such as immune response,thrombosis and tumor metastasis and provides a new idea for the development of anti-inflammation,anti-thrombosis and anti-tumor drugs.