Am. J. Respir. Crit. Care Med., Volume 157, Number 2, February 1998, 599-609

Differential Contribution of Various Adhesion Molecules to Leukocyte Kinetics in Pulmonary Microvessels of Hyperoxia-exposed Rat Lungs

KAZUMI NISHIO, YUKIO SUZUKI, TAKUYA AOKI, KOICHI SUZUKI, ATSUSHI MIYATA, NAGATO SATO, KATSUHIKO NAOKI, HIROYASU KUDO, HARUKUNI TSUMURA, HIROSHI SERIZAWA, SHIGEAKI MOROOKA, YUZURU ISHIMURA, MAKOTO SUEMATSU, and KAZUHIRO YAMAGUCHI

Departments of Medicine and Biochemistry, School of Medicine, Keio University, Tokyo; Department of Internal Medicine, Kitasato Institute Hospital, Tokyo; Biomedical Department, Sankei Corporation, Tokyo; and Sumitomo Pharmaceutical Research Center, Osaka, Japan

To elucidate the differential role of various adhesion molecules in distorting leukocyte behavior in the microvasculature of hyperoxia-exposed rat lungs, we investigated fluorescein-labeled leukocyte and erythrocyte kinetics in isolated lungs taken from the animals exposed to 90% O₂ for 48 h under conditions in which endothelial intercellular adhesion molecule-1 (ICAM-1) and P-selectin were inhibited by appropriate monoclonal antibodies (1A29 for ICAM-1 and ARP2-4 for P-selectin), while leukocyte L-selectin was restrained with fucoidin. Measurements of blood cell kinetics were made by a confocal laser luminescence microscope coupled with a high-speed video camera. In addition, we histologically examined leukocyte accumulation within the alveolar septa and ICAM-1 as well as P-selectin expressions in the lung. We found that P-selectin expression was sparsely enhanced only in arterioles, whereas ICAM-1 was significantly induced in both venules and capillaries. Firm adhesion of leukocytes was not identified in arterioles and venules, whereas leukocyte rolling was evident in both the vessels. Arteriolar rolling was regulated via a P-selectin- and ICAM-1-independent but L-selectin-dependent mechanism, whereas venular rolling was mediated via a P-selectin-independent but ICAM-1- and L-selectin-dependent pathway. Leukocyte sequestration within capillaries was augmented by an ICAM-1-related mechanism. These findings may suggest that, in hyperoxia-exposed lungs, induction of adhesion molecules and their obstacles to leukocyte behavior are qualitatively different among arterioles, venules, and capillaries.

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