Modulation of human polymorphonuclear neutrophil functions by alpha 1-acid glycoprotein
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E Lainé1, R Couderc, M Roch-Arveiller
1Département de Pharmacologie, CNRS URA 595, France.
Abstract:
alpha 1-Acid glycoprotein (alpha 1-AGP), a naturally occurring human plasma protein and acute-phase reactant, was extracted by a two-step procedure from sera collected from four healthy men. Its activity was tested in vitro on human polymorphonuclear (PMN) functions (migration, aggregation, O2- generation). alpha 1-AGP was not chemoattractant but inhibited the PMN response to the chemoattractant formylmethionyl-leucyl-phenylalanine without affecting spontaneous migration (Boyden and agarose methods of assessment). At concentrations between 0.15 and 0.45 mg/ml, alpha 1-AGP exerted an aggregating effect with a maximal effective concentration of 0.3 mg/ml. alpha 1-AGP inhibited superoxide generation by PMNs stimulated either by opsonized zymosan or phorbol myristate acetate. This inhibition varied according to the intensity of the stimulation. At low stimulus concentrations, a dose-dependent inhibition of membrane-associated PMN responsiveness to soluble or particulate stimuli was observed. These findings suggest that alpha 1-AGP may be able to prevent PMN activation in the course of inflammatory processes in vivo.
Insights
Alpha 1-Acid glycoprotein (alpha 1-AGP) inhibits human polymorphonuclear cell functions, including migration and superoxide generation. This suggests alpha 1-AGP may prevent inflammatory cell activation in vivo.
Area of Science:
- Immunology
- Biochemistry
Background:
- Alpha 1-Acid glycoprotein (alpha 1-AGP) is a human plasma protein and an acute-phase reactant.
- Its role in modulating immune cell function requires further investigation.
Purpose of the Study:
- To investigate the in vitro effects of alpha 1-AGP on human polymorphonuclear (PMN) functions.
- To determine if alpha 1-AGP modulates PMN responses to stimuli.
Main Methods:
- Alpha 1-AGP was extracted from healthy human sera using a two-step procedure.
- In vitro assays assessed PMN migration (Boyden and agarose methods), aggregation, and superoxide generation (stimulated by zymosan or phorbol myristate acetate).
Main Results:
- Alpha 1-AGP did not exhibit chemoattractant properties but inhibited PMN migration towards formylmethionyl-leucyl-phenylalanine.
- It induced PMN aggregation at concentrations of 0.15-0.45 mg/ml, with maximal effect at 0.3 mg/ml.
- Alpha 1-AGP inhibited superoxide generation in a dose-dependent manner, particularly at lower stimulus concentrations.
Conclusions:
- Alpha 1-AGP modulates key human PMN functions, including migration, aggregation, and superoxide generation.
- These findings suggest a potential role for alpha 1-AGP in preventing excessive PMN activation during inflammatory processes.