Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability.
Many diseases have an inflammatory component, where neutrophil interactions with the vascular endothelium lead to barrier dysfunction and increased permeability. Neutrophils increase permeability through secreted products such as the chemokines CXCL1, 2, 3, and 8, through adhesion-dependent processes involving beta(2) integrins interacting with endothelial ICAM-1, and through combinations where beta(2) integrin engagement leads to degranulation and secretion of heparin-binding protein. Some neutrophil products, such as arachidonic acid or the leukotriene LTA4, are further processed by endothelial enzymes via transcellular metabolism before the resulting products thromboxane A2 or LTC4 can activate their cognate receptors. Neutrophils also generate reactive oxygen species that induce vascular leakage. This review focuses on the mechanisms of neutrophil-mediated leakage.
DiStasi
Matthew R
MR
La Jolla Institute of Allergy & Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
Ley
Klaus
K
D000818:Animals; D002199:Capillary Permeability / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D016023:Integrins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide