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Am J Physiol Heart Circ Physiol 273: H2361-H2371, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 5, H2361-H2371, November 1997

Role of CD18-ICAM-1 in the entrapment of stimulated leukocytes in alveolar capillaries of perfused rat lungs

Takuya Aoki1, Yukio Suzuki3, Kazumi Nishio1, Kouichi Suzuki1, Atsusi Miyata1, Yutaka Iigou5, Hiroshi Serizawa3, Harukuni Tsumura4, Yuzuru Ishimura2, Makoto Suematsu2, and Kazuhiro Yamaguchi1

Departments of 1 Internal Medicine and 2 Biochemistry, School of Medicine, Keio University, Tokyo 160; 3 Department of Internal Medicine, Kitasato Institute Hospital, Tokyo 108; 4 Biomedical Department, Sankei Corporation, Tokyo 113; and 5 New Product Research Laboratories IV, Daiichi Pharmaceutical Company, Tokyo 134, Japan

This study aimed to examine the behavior of stimulated leukocytes in the pulmonary microcirculation. The leukocyte-endothelium interaction was visualized under physiological shear rates in perfused rat lungs using high-speed confocal laser video microscopy. Leukocytes labeled with carboxyfluorescein were stimulated with cytokine-induced neutrophil chemoattractant (CINC/gro), which caused L-selectin shedding and inverse upregulation of CD18. Neither unstimulated nor stimulated leukocytes exhibited rolling in either pulmonary arterioles or venules, whereas both were sequestered in capillaries. Approximately 50% of stimulated leukocytes showed a transient cessation of movement in pulmonary capillaries. The CINC/gro stimulation, which inhibited leukocyte rolling and adhesion to mesenteric venules, reduced leukocyte velocity and increased leukocytes in pulmonary capillaries. Pretreatment with monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1) or CD18 attenuated these changes. Confocal microfluorography revealed constitutive expression of ICAM-1 not only in venules but also abundantly in capillary networks. These results suggest that selectin-independent, CD18-ICAM-1-dependent capillary sequestration is one of the major mechanisms by which activated leukocytes accumulate in the lungs.

pulmonary microcirculation; mesenteric microcirculation; L-selectin; leukocyte adhesion; leukocyte plugging


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