Am. J. Respir. Crit. Care Med., Volume 161, Number 5, May 2000, 1681-1688

Roles of ICAM-1 for Abnormal Leukocyte Recruitment in the Microcirculation of Bleomycin-induced Fibrotic Lung Injury

NAGATO SATO, YUKIO SUZUKI, KAZUMI NISHIO, KOICHI SUZUKI, KATSUHIKO NAOKI, KEI TAKESHITA, HIROYASU KUDO, NAOKI MIYAO, HARUKUNI TSUMURA, HIROSHI SERIZAWA, MAKOTO SUEMATSU, and KAZUHIRO YAMAGUCHI

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

To assess the importance of endothelial intercellular adhesion molecule-1 (ICAM-1) in microvascular leukocyte kinetics in diseased lungs, we investigated the transitional changes in ICAM-1 expression, vascular diameter, and leukocyte behavior in rat pulmonary microcirculation during the development of acute lung injury (ALI) and chronic fibrosis (FIB) evoked by bleomycin (BLM). Observations were made in the isolated perfused lung with a real-time confocal laser luminescence microscope. Microvascular cell kinetics were evaluated by measuring the behavior of fluorescence- labeled leukocytes and erythrocytes in the presence or absence of anti-ICAM-1 monoclonal antibody (1A29). Arteriolar ICAM-1 showed little change at any time after BLM treatment. Venular ICAM-1 was first enhanced at the initial phase of ALI followed by the second upregulation at the early phase of FIB. Capillary ICAM-1 showed a sustained increase at both ALI and FIB. Arteriolar and venular diameters were not altered but capillary diameter decreased during ALI and early FIB stages. Although firm adherence of leukocytes to arteriolar and venular walls was not observed, rolling leukocytes were increased in venules both at the initial phase of ALI and at the early phase of FIB. The leukocyte rolling in venules correlated well with transitional changes in ICAM-1 and was inhibited by 1A29. Sustained entrapment of leukocytes in capillaries was attributed to changes in vascular diameter as well as augmented ICAM-1. In conclusion, ICAM-1 plays an important role in microvascular leukocyte recruitment in both ALI and FIB in the BLM-injured lung.

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