An assessment of the effects of glucocorticoids on degranulation, chemotaxis, binding to vascular endothelium and formation of leukotriene B4 by purified human neutrophils

R. P. Schleimer, H. S. Freeland, S. P. Peters, K. E. Brown, C. P. Derse

Research output: Contribution to journalArticlepeer-review

Abstract

Glucocorticoids exert their actions through a time-dependent receptor-mediated, protein synthesis- and RNA synthesis-dependent mechanism. We have assessed the effects of 24-h culture of human neutrophils with dexamethasone on degranulation, chemotaxis, binding to vascular endothelium and formation of leukotriene B4. Purified neutrophils contained an average of 2896 [3H]dexamethasone binding sites per cell with a K(d) of 4.1 x 10-9 M for [3H]dexamethasone binding. Cells exposed to dexamethasone (10-6 M) released equal or greater quantities of the lysosomal enzymes, lysozyme and β-glucuronidase in response to formylmethionyl-leucyl-phenylalanine, serum activated zymosan, and the tumor promoting phorbol diester 12-O-tetradecanoylphorbol-13-acetate compared to controls. Culture with dexamethasone also did not inhibit neutrophil chemotaxis in response to a range of concentrations of formylmethionyl-leucyl-phenylalanine, or did it inhibit binding of neutrophils to cultured endothelial cells stimulated by either leukocyte activators (formylmethionine-leucyl-phenylalanine and platelet-activating factor) or endothelial activators (interleukin-1, lipopolysaccharide or 12-O-tetradecanoylphorbol-13-acetate). Spontaneous adherence of neutrophils to endothelial cells was inhibited (82.9 ± 6.8% of control, P < .025, n = 18). Neither in vitro or in vivo glucocorticoids inhibited neutrophil leukotriene B4 formation induced by either the calcium ionophore A23187 or serum activated zymosan. We conclude that human neutrophils are not functionally inactivated by glucocorticoids and suggest that the mechanism by which glucocorticoids inhibit neutrophil accumulation at inflammatory sites may be by inhibition of the production of chemoattractants and endothelial activators rather than inhibition of their actions.

Original languageEnglish (US)
Pages (from-to)598-605
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume250
Issue number2
StatePublished - Jan 1 1989

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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