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Alteration of neutrophil (PMN) function by heparin, dexamethasone, and enalapril
J A Freischlag1, M D Colburn, W J Quiñones-Baldrich
1Section of Vascular Surgery, UCLA School of Medicine.
Abstract:
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)
Insights
Heparin, dexamethasone, and enalapril inhibit neutrophil chemotaxis. Heparin and enalapril reduce phagocytosis, while dexamethasone stimulates it, impacting neutrophil function.
Area of Science:
- Immunopharmacology
- Cellular immunology
Background:
- Intimal hyperplasia is a pathological process.
- Certain pharmacologic agents may suppress intimal hyperplasia.
- Neutrophil (PMN) function plays a role in vascular responses.
Purpose of the Study:
- To investigate the effect of heparin, dexamethasone, and enalapril on human neutrophil function.
- To assess the impact of these agents on superoxide anion production, chemotaxis, and phagocytosis.
Main Methods:
- Human neutrophils were isolated and exposed to varying concentrations of heparin, dexamethasone, or enalapril.
- Superoxide anion production was measured using spectrophotometry.
- Neutrophil chemotaxis and phagocytosis assays were performed using a Neuro Probe chamber and opsonized zymosan particles, respectively.
Main Results:
- None of the agents significantly altered superoxide anion production.
- All three agents significantly inhibited neutrophil chemotaxis at all tested doses.
- Heparin and enalapril reduced phagocytic activity, whereas dexamethasone significantly stimulated it.
Conclusions:
- Heparin, dexamethasone, and enalapril differentially affect neutrophil functions.
- These agents inhibit neutrophil chemotaxis, suggesting a potential role in modulating inflammatory responses.
- The opposing effects on phagocytosis highlight the complex immunomodulatory actions of these drugs.