肺微小循環の白血球動態に対する細胞接着分子の関与

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

　正常ラットより作成した灌流肺を用いて肺細葉内細動脈，細静脈，毛細血管における白血球動態を観察し，細胞接着分子の関与を解析した．肺微小血管径および白血球動態の観察は共焦点レーザー顕微鏡を用いて行った．白血球と血管内皮細胞の相互作用による白血球速度の低下（ローリング現象）は細動静脈で認められたが，細動脈でより高度であった．細動脈における無刺激白血球ローリング現象はL—セレクチン依存性，細静脈におけるそれはICAM−1依存性であった．無刺激白血球の毛細血管内粘着現象への細胞接着分子の関与は少なかった．cytokine-induced neutrophil chemoattractant／gro（CINC／gro）刺激で細胞表面のCD 11／CD 18の発現を増加させた白血球の細静脈ローリング数および毛細血管内粘着数は有意に増加した．以上の結果より正常肺微小血管での白血球動態には細動脈と細静脈・毛細血管で異なった細胞接着分子が関与すると考えられた．

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 arter-ioles, venules and capillaries under conditions in which functions of adhesion molecules were appropriately inhibited. Observation of leukocyte behavior and deter-mination 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 interactionsbetween the endothelium and the leukocyte was inves-tigated 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 mole-cules including ICAM-1 as well as P-and L-selectins. Stimulation of leukocytes with cvtokine - 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 in-I eluding arterioles, venules and capillaries is modified by different classes of adhesion molecules.