Chemoattractant signals and beta 2 integrin occupancy at apical endothelial contacts combine with shear stress signals to promote transendothelial neutrophil migration.
Lymphocyte transendothelial migration (TEM) is promoted by fluid shear signals and apical endothelial chemokines. Studying the role of these signals in neutrophil migration across differently activated HUVEC in a flow chamber apparatus, we gained new insights into how neutrophils integrate multiple endothelial signals to promote TEM. Neutrophils crossed highly activated HUVEC in a beta(2) integrin-dependent manner but independently of shear. In contrast, neutrophil migration across resting or moderately activated endothelium with low-level beta(2) integrin ligand activity was dramatically augmented by endothelial-presented chemoattractants, conditional to application of physiological shear stresses and intact beta(2) integrins. Shear stress signals were found to stimulate extensive neutrophil invaginations into the apical endothelial interface both before and during TEM. A subset of invaginating neutrophils completed transcellular diapedesis through individual endothelial cells within <1 min. Our results suggest that low-level occupancy of beta(2) integrins by adherent neutrophils can mediate TEM only if properly coupled to stimulatory shear stress and chemoattractant signals transduced at the apical neutrophil-endothelial interface.
Cinamon
Guy
G
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Shinder
Vera
V
Shamri
Revital
R
Alon
Ronen
R
D018821:CD18 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure*; D010972:Platelet Activating Factor / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D012212:Rheology; D015398:Signal Transduction / Q000276:immunology*; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018821:CD18 Antigens; D002630:Chemotactic Factors; D010972:Platelet Activating Factor; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha