Endogenous corticosteroids mediate the neutrophilia caused by platelet-activating factor in the mouse.
Platelet-activating factor (PAF; 100 ng i.v.) transiently modified the number of circulating neutrophils in the mouse, inducing a fast neutropenia (2 min) followed by a late onset neutrophilia (2 h). The potential involvement in PAF-induced neutrophilia of granulocytotic agents such as interleukin-1 and tumor necrosis factor-alpha could be excluded on the basis of the ineffectiveness of interleukin-1 receptor antagonist and of a specific monoclonal antibody anti-murine tumor necrosis factor-alpha. PAF granulocytosis was preceded by a significant rise in plasma corticosterone at 20 min. The involvement of endogenous corticosteroids was confirmed by the experiments with adrenalectomized mice and in animals pretreated with the steroid antagonist RU486 (11 beta-(4-dimethyl amino-phenyl) 17 beta-hydroxy, 17 alpha(prop-1-ynyl) estra 4,9-dien-3-one), where PAF-induced neutrophilia was greatly reduced (approximately 50%). Moreover, sustained increase in plasma corticosterone by administration of adrenocorticotropic hormone was paralleled by an intense neutrophilia. We show evidence that endogenous corticosterone acts through the glucocorticoid-inducible protein lipocortin 1.
D000305:Adrenal Cortex Hormones / Q000097:blood / Q000494:pharmacology*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D017305:Annexin A1 / Q000187:drug effects; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015735:Mifepristone / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011863:Radioimmunoassay; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D017305:Annexin A1; D010972:Platelet Activating Factor; D015735:Mifepristone; D000324:Adrenocorticotropic Hormone