Prednisolone interferes with neutrophil adhesion and neutrophil mediated endothelial injury.
Adhesion of leukocytes to vascular endothelium is a crucial step in inflammation. This interaction may result in damage of the endothelial cells (EC). We evaluated the effects of prednisolone on adhesive interactions between human polymorphonuclear neutrophil granulocytes (PMN) and human umbilical vein endothelial cells (HUVEC) as well as PMN mediated cytotoxicity to HUVEC (as release of 51chromium), mediated by N-formyl-methionyl-leucyl-phenylalanine (fMLP), lipoxin A4 (LXA4), and the calcium ionophore A23187 in vitro. Prednisolone dose-dependently interfered with adhesion and cytotoxicity induced by fMLP. Prednisolone (at 10 microM) led to a 39% reduction of adhesion and an almost complete inhibition of cytotoxicity, mainly by effects on the PMN. Prednisolone also interfered with cytotoxicity induced by LXA4 by effects on PMN as well as on HUVEC. Adhesion and cytotoxicity induced by the calcium ionophore A23187 was not affected in any way by prednisolone. Thus, in these in vitro models of vasculitis, prednisolone interferes with adhesive and cytotoxic interactions induced by receptor-dependent agonists. These protective effects of prednisolone might explain some of the beneficial effects of glucocorticoids in the treatment of vasculitis.
Bratt
J
J
Department of Rheumatology, The Karolinska Institute at Huddinge University Hospital, Sweden.
Heimbürger
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D044045:Lipoxins; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011239:Prednisolone / Q000494:pharmacology*; D014471:Umbilical Veins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; C040527:lipoxin A4; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011239:Prednisolone