Neutrophil recruitment under shear flow: it's all about endothelial cell rings and gaps.
Leukocyte recruitment to tissues and organs is an essential component of host defense. The molecular mechanisms controlling this process are complex and remain under active investigation. The combination of biochemical techniques and live cell imaging using in vivo and in vitro flow-model approaches have shed light on several aspects of neutrophil transmigration through the vascular endothelial lining of blood vessels. Here, we focus on the role of adhesion molecule signaling in endothelial cells and their downstream targets during the process of transendothelial migration at cell-cell borders (paracellular transmigration). An emerging model involves the leukocyte beta2 integrin engagement of endothelial cell ICAM-1, which triggers integrin-ICAM-1 clustering (rings) and stabilizes leukocyte adhesion at cell-cell junctions. This step recruits nonreceptor tyrosine kinases that phosphorylate key tyrosine residues in the cytoplasmic tail of VE-cadherin, which destabilizes its linkage to catenins and the actin cytoskeleton, triggering the transient opening of VE-cadherin homodimers to form a gap in the cell junction, through which the neutrophil transmigrates. Interestingly, the signaling events that lead to neutrophil transmigration occur independently of shear flow in vitro.
Alcaide
Pilar
P
Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Auerbach
Scott
S
Luscinskas
Francis W
FW
D000199:Actins / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D015820:Cadherins / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D003599:Cytoskeleton / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007365:Intercellular Junctions / Q000276:immunology; D018448:Models, Immunological; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D033081:Shear Strength; D015398:Signal Transduction / Q000276:immunology*; D000099152:Cadherin 5
D000199:Actins; D015703:Antigens, CD; D018821:CD18 Antigens; D015820:Cadherins; D018799:Intercellular Adhesion Molecule-1; D000099152:Cadherin 5