Alteration of neutrophil (PMN) function by heparin, dexamethasone, and enalapril.
The aim of this study is to investigate the effect of a seemingly divergent class of pharmacologic agents, each having been reported to suppress intimal hyperplasia, on neutrophil (PMN) function. Human PMNs were isolated and exposed for 30 min to either saline or one of three different pharmacologic agents, each tested at three different concentrations: Group 1, saline (control, n = 14); Groups 2-4, heparin (5000 units, n = 8; 2500 units, n = 6; 1250 units, n = 6) respectively; Groups 5-7, dexamethasone (4 mg, n = 8; 2 mg, n = 6; 1 mg, n = 6), respectively; and Groups 8-10, enalapril (1.25 mg, n = 8; 0.62 mg, n = 6; 0.31 mg, n = 6). Superoxide anion production was measured by the reduction of cytochrome c in a spectrophotometric assay. Chemotaxis was evaluated by the number of PMNs migrating across a filter using a Neuro Probe chamber. Phagocytosis was determined by the ingestion of opsonized zymosan particles by PMNs. Serum obtained from each PMN donor was used both to opsonize the zymosan and as a chemoattractant in the chemotaxis assay. No agent, at any dose, significantly changed superoxide production when compared to control cells. All three agents significantly inhibited PMN chemotaxis at every dose tested (P less than 0.01). In the phagocytosis assay, both heparin (at high and intermediate doses) and enalapril (at all doses) significantly reduced phagocytic activity (P less than 0.01); however, dexamethasone (at high and intermediate doses) produced a marked stimulation (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Freischlag
J A
JA
Section of Vascular Surgery, UCLA School of Medicine.
Colburn
M D
MD
Quiñones-Baldrich
W J
WJ
Moore
W S
WS
D000838:Anions / Q000037:antagonists & inhibitors / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
D000838:Anions; D013481:Superoxides; D004656:Enalapril; D003907:Dexamethasone; D006493:Heparin