ICAM-1-Coupled Cytoskeletal Rearrangements and Transendothelial Lymphocyte Migration Involve Intracellular Calcium Signaling in Brain Endothelial Cell Lines

摘要: Endothelium of the cerebral blood vessels, which constitutes blood-brain barrier, controls adhesion and trafficking leukocytes into brain. Investigating signaling pathways triggered by engagement molecules expressed on brain endothelial cells using two rat cell lines (RBE4 GP8), we report in this paper that ICAM-1 cross-linking induces a sustained tyrosine phosphorylation phosphatidylinositol-phospholipase C (PLC)γ1, with concomitant increase both inositol phosphate production intracellular calcium concentration. Our results suggest PLC are responsible, via calcium- protein kinase (PKC)-dependent pathway, for p60Src activation substrate, cortactin. PKCs also required cytoskeleton-associated proteins, focal paxillin, but not ICAM-1-coupled p130Cas phosphorylation. PKC’s is necessary stress fiber formation induced cross-linking. Finally, pretreatment chelator or PKC inhibitors significantly diminishes transmonolayer migration activated T lymphocytes, without affecting their to cells. In summary, our data demonstrate which, PKCs, mediates actin-associated proteins cytoskeletal rearrangement lines. indicate these calcium-mediated events essential lymphocyte through barrier.