SECRETED GLUCOCORTICOIDS REGULATE LEUKOCYTE-ENDOTHELIAL INTERACTIONS IN INFLAMMATION - A DIRECT VITAL MICROSCOPIC STUDY

Leukocytes come into intimate contact with the venular endothelium as they extravasate from blood to the interstitium during inflammation, I n exteriorized tissues, the number of leukocytes rolling along the ves sel wall was markedly increased in adrenalectomized and metyrapone-tre ated animals, relative to sham-operated and normal animals, During the development of an acute, local inflammatory response, rollers were nu merically decreased and a stronger adhesion of the cells to the endoth elium, with a concomitant migration into tissues, was observed, Adhesi on and mig-ration were much more marked in adrenalectomized and metyra pone-treated animals than in controls, suggesting that secreted glucoc orticoids exert a suppressive effect on leukocyte-endothelial interact ions, The increased number of rolling leukocytes in adrenalectomized a nd metyrapone-treated animals apparently resulted in more cells availa ble to migrate into inflamed tissues. The effect appears to involve re ceptor occupancy and induction of gene expression because normal anima ls receiving the steroid antagonist RU 38 486, actinomycin D, or cyclo heximide behaved as adrenalectomized or metyrapone-treated animals, Ad ministration to adrenalectomized animals of a monoclonal antibody to t he membrane glycoprotein complex CD18 did not affect the number of rol ling cells, but dramatically reduced the number of adherent or migrate d leukocytes. It is suggested that secreted glucocorticoids, in additi on to an effect on rolling behavior of circulating leukocytes, might a lso modulate the activity of the glycoprotein complex CD18 on white bl ood cells. The ultimate consequence is a restrictive effect on cell em igration in inflammation.