Thromboxane-induced neutrophil adhesion to pulmonary microvascular and aortic endothelium is regulated by CD18.
Thromboxane (Tx) A2 generation and subsequent selective pulmonary sequestration of neutrophils (PMNs) is characteristic of several forms of the adult respiratory distress syndrome (ARDS). Therefore, we examined PMN-dependent adhesion to cultured pulmonary microvessel and aortic endothelium (EC) in response to U46,619 (Tx mimic). Nonstimulated PMNs were two fold more adherent to pulmonary microvessel EC than to aortic EC (P less than 0.01). PMN pretreatment with Tx mimic (10(-6) M) increased adhesion to both types of EC (P less than 0.01). The Tx mimic-induced adhesion was blocked by receptor antagonists to Tx (SQ29,548) and to leukotrienes (FPL55,712), and by the anti-CD18 mAb TS1/18 (P less than 0.01, all cases). Baseline PMN adhesion also was modulated by Tx, leukotrienes, and CD18, for both EC types. These results indicate pulmonary microvessel EC is intrinsically more adhesive for both nonstimulated and stimulated PMNs than aortic EC and that Tx mediates PMN-dependent adhesion by coupled interaction of Tx and LT receptors via CD18 activation.
Laboratory for Microvascular Research, Biological Science Center, Boston University, Massachusetts 02215.
M E
ME
Wiles
R
R
Welbourn
G
G
Goldman
H B
HB
Hechtman
D
D
Shepro
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001011:Aorta / Q000187:drug effects / Q000276:immunology*; D018821:CD18 Antigens; D002196:Capillaries / Q000276:immunology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D007975:Leukotriene B4 / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000276:immunology*; D008833:Microcirculation / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000187:drug effects; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D018102:Receptors, Leukotriene B4; D013928:Thromboxane A2 / Q000502:physiology*
D015703:Antigens, CD; D018821:CD18 Antigens; D011450:Prostaglandin Endoperoxides, Synthetic; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid