Behavior of stimulated leukocytes in the pulmonary microcirculation of perfused rat lungs

To investigate the dynamics of activated leukocytes and the roles of CD18-ICAM-1 pathway, we examined the effects of rat IL-8 and monoclonal antibodies (mAbs) against CD18 and ICAM-1 on the behavior of leukocytes in microvessels of perfused rat lungs. Specific pathogen free male Sprague-Dawley rats were used. Perfused rat lungs were prepared so as to obtain stable physiological shear rates. We used a confocal laser scanning microscope equipped with a high speed video analysis system to visualize pulmonary microcirculation. Rat leukocytes were activated with rat IL-8. No rolling leukocytes were observed in either pulmonary arterioles or venules, and leukocytes were sequestered in capillaries. The majority of unstimulated capillary leukocytes moved smoothly. About 50% of stimulated leukocytes, however, showed a transient cessation of movement in pulmonary capillaries. Rat IL-8 decreased the relative leukocyte velocities against mean blood velocities in capillaries (45%) and venules (65%), and increased intracapillary neutrophils. Anti-CD18 and anti-ICAM-1 mAbs attenuated these changes. These results suggest that unique features exist in the interaction between activated leukocytes and pulmonary microvessels, and that CD18-ICAM-1-dependent capillary sequestration is one of the major mechanisms by which activated leukocytes accumulate in lungs.