Thromboxane-induced neutrophil adhesion to pulmonary microvascular and aortic endothelium is regulated by CD18

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Abstract
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 HC than to aortic EC (P < 0.01). PMN pretreatment with Tx mimic (10−6 M) increased adhesion to both types of EC (P < 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 < 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 CD 18 activation.

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