Secreted glucocorticoids regulate leukocyte-endothelial interactions in inflammation. A direct vital microscopic study

Abstract

Leukocytes come into intimate contact with the venular endothelium as they extravasate from blood to the interstitium during inflammation. In exteriorized tissues, the number of leukocytes rolling along the vessel wall was markedly increased in adrenalectomized and metyrapone-treated animals, relative to sham-operated and normal animals. During the development of an acute, local inflammatory response, rollers were numerically decreased and a stronger adhesion of the cells to the endothelium, with a concomitant migration into tissues, was observed. Adhesion and migration were much more marked in adrenalectomized and metyrapone-treated animals than in controls, suggesting that secreted glucocorticoids exert a suppressive effect on leukocyte-endothelial interactions. The increased number of rolling leukocytes in adrenalectomized and metyrapone-treated animals apparently resulted in more cells available to migrate into inflamed tissues. The effect appears to involve receptor occupancy and induction of gene expression because normal animals receiving the steroid antagonist RU 38 486, actinomycin D, or cycloheximide behaved as adrenalectomized or metyrapone-treated animals. Administration to adrenalectomized animals of a monoclonal antibody to the membrane glycoprotein complex CD18 did not affect the number of rolling cells, but dramatically reduced the number of adherent or migrated leukocytes. It is suggested that secreted glucocorticoids, in addition to an effect on rolling behavior of circulating leukocytes, might also modulate the activity of the glycoprotein complex CD18 on white blood cells. The ultimate consequence is a restrictive effect on cell emigration in inflammation.

A Potential Role for Annexin 1 as a Physiologic Mediator of Glucocorticoid-Induced L-Selectin Shedding from Myeloid Cells

“…Recent work suggests that glucocorticoid-induced inhibition of neutrophil accumulation is mediated by an effect on the initial steps of the process (10). Therefore, it has been suggested that glucocorticoid-induced shedding of L-selectin may be one mechanism by which glucocorticoids inhibit neutrophil accumulation in vivo.…”

Anti-inflammatory activity of craterostigma pumilum (hochst) is associated with hyperalgesia

“…aspirin and diclofenac. They inhibit prostaglandin synthesis (Vane, 2000) and steroids that target migration and ultimately degranulation of leukocytes (Farsky et al, 1995). In this study, the edema was obliterated by prior administration of 15 mg of diclofenac sodium 30 minutes prior to injection with formalin.…”

Estudo dos mecanismos de ação da hidroquinona e fenol sobre o recrutamento leucocitário em respostas inflamatórias

“…Esta resposta via Th2 é 33 mediada pela produção de EROs e citocinas como: IL-4, IL-5 e IL-13. As alterações que caracterizam a asma alérgica são: elevada IgE sérica, intensa secreção de muco, eosinofilia e exacerbada reatividade brônquica (MATTES et al, 2002;HYLKEMA et al, 2002;CAREAU et al, 2002 (ALI et al, 1999;FRANGOGIANNIS et al, 2001;KUBES, 2002 (DAHLEN et al, 1981;FORTES et al, 1991;FARSKY et al, 1995FARSKY et al, , 2004.…”

“…These leukocytes moved sufficiently slowly to be individually visible and were counted as they rolled past a selected point on one side of the vessel. The number of leukocytes adhering to the endothelium (stopped at the vessel wall) was determined at the same vascular segment (Dahlen et al, 1981;Fortes et al, 1991;Farsky et al, 1995Farsky et al, , 2004.…”