Modification of Leukocyte Kinetics in Normal Pulmonary Microcirculation Caused by Adhesion Molecules

In order to elucidate the possible roles of various adhesion molecules in modifying the leukocyte behavior in the pulmonary microcirculation, we investigated, based on the isolated perfused lungs prepared from normal rats, the leukocyte kinetics in pulmonary arterioles, venules and capillaries under conditions in which functions of adhesion molecules were appropriately inhibited. Observation of leukocyte behavior and determination of microvascular architecture were precisely made by using a real-time confocal laser luminescence microscope. All the confocal images thus obtained were recorded on a high-speed and high-sensitivity video camera. The significant reduction in leukocyte velocity (i. e. leukocyte rolling) due to interfering interactions between the endothelium and the leukocyte was investigated in both arterioles and venules. However, the relative frequency of leukocytes with rolling was much higher in arterioles than that in venules Arteriolar rolling of unstimulated leukocytes was mediated via a L -selectin dependent mechanism, while venular rolling was governed by an ICAM-1 related mechanism. The entrapment of unstimulated leukocytes in capillaries was not conspicuously influenced by any adhesion molecules including ICAM-1 as well as P-and L-selectins. Stimulation of leukocytes with cytokine - induced neutrophil chemoattractant/gro (CINC/gro) which upregulates CD 11/CD 18 on the leukocyte surface significantly enhanced the numbers of rolling leukocytes in venules and of entrapped leukocytes in capillaries. These experimental results may suggest that leukocyte kinetics in the normal pulmonary microcirculation including arterioles, venules and capillaries is modified by different classes of adhesion molecules.