DO ADHESION MOLECULES IMPORTANTLY REGULATE LEUKOCYTE KINETICS WITHIN INTRAACINAR MICROVESSELS OF THE LUNG

Precise assessment of blood cell kinetics in the pulmonary microcircul ation is extremely difficult because pulmonary microvascular architect ure contains arterioles, venules and capillaries in an exceedingly int ricate and densely convoluted fashion. Conventional epiluminescence mi croscopy may not be suitable for investigation of blood cell kinetics in the pulmonary microcirculation, in which arterioles, venules and ca pillary networks are not located in the same plane. To overcome these impediments, we recently developed a real-time confocal laser luminesc ence microscope with a high-speed analysis component having the capaci ty to yield confocal-images of rapidly moving cells at a rate of 1,000 frames/sec and at sufficiently high magnification. In the current rev iew, we will first introduce the details of our newly developed observ ation system constructed with a view to estimation of blood cell dynam ics in the intraacinar microcirculation of the lung. Applying this nov el method to isolated perfused rat lungs, we will secondly address the issue of whether or not leukocyte-endothelium interactions in the pul monary microcirculation qualitatively differ from those serving in the systemic microcirculation. We will particularly shed light on possibl e roles of endothelial ICAM-1, endothelial P-selectin and leukocyte L- selectin in distorting leukocyte kinetics in the intraacinar microvess els under a variety of diseased conditions, including prolonged exposu re to a hyperoxic environment inducing a significant upregulation of I CAM-1 as well as P-selectin on the pulmonary microvascular endothelium , and stimulation of leukocytes by an IL-8 analog causing downregulati on of leukocyte L-selectin but inverse upregulation of CD18-related in tegrins.