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Atrial natriuretic factor stimulates migration by human neutrophils
1Department of Medical Biochemistry, University of Leiden, Netherlands.
European Journal of Pharmacology
|February 15, 1995
Summary
Atrial natriuretic factor (ANF) significantly boosts human neutrophil migration, involving both chemokinetic and chemotactic actions. This effect is partly mediated by a novel ANF receptor pathway independent of cyclic GMP.
Area of Science:
- Immunology
- Cell Biology
- Physiology
Background:
- Atrial natriuretic factor (ANF) is a hormone primarily involved in cardiovascular and renal regulation.
- Neutrophil migration is a critical process in innate immunity and inflammation.
- The signaling pathways by which ANF influences immune cell function are not fully elucidated.
Purpose of the Study:
- To investigate the effect of atrial natriuretic factor (ANF) on human neutrophil migration.
- To elucidate the signaling mechanisms underlying ANF-mediated neutrophil chemotaxis and chemokinesis.
- To explore the role of cyclic GMP (cGMP) and G-protein coupled receptors in ANF-induced neutrophil responses.
Main Methods:
- Human neutrophils were stimulated with varying concentrations of ANF.
- Neutrophil migration assays (chemotaxis and chemokinesis) were performed.
- Intracellular cyclic GMP (cGMP) levels were measured.
- The effects of soluble guanylate cyclase inhibitors, pertussis toxin, and guanosine-5'-[gamma thio]triphosphate (GTPγS) were assessed.
Main Results:
- ANF significantly stimulated human neutrophil migration in a concentration-dependent manner (4 x 10(-9) to 10(-7) M).
- The ANF effect was dependent on extracellular Mg2+ but not Ca2+.
- ANF enhanced neutrophil cyclic GMP (cGMP) levels.
- Inhibitors of soluble guanylate cyclase did not block ANF-stimulated migration, but pertussis toxin did.
- GTPγS synergistically enhanced ANF-induced migration, suggesting involvement of a G-protein coupled receptor pathway.
- A subset of ANF's effect on migration appears independent of cGMP modulation.
Conclusions:
- Atrial natriuretic factor (ANF) is a potent stimulator of human neutrophil migration.
- ANF-induced neutrophil migration involves both chemokinetic and chemotactic components.
- While ANF modulates cGMP levels, a significant portion of its effect on neutrophil migration is mediated through a pertussis toxin-sensitive pathway, likely involving an ANF receptor subtype that does not activate guanylate cyclase.