ATRIAL-NATRIURETIC-FACTOR STIMULATES MIGRATION BY HUMAN NEUTROPHILS

Atrial natriuretic factor causes a strong stimulation of human neutrophil migration in the concentration range of 4 x 10(-9) and 10(-7) M. The effect, which depends on the presence of extracellular Mg2+ but not on extracellular Ca2+, is composed of a chemokinetic and a chemotactic component. Cyclic GMP level of neutrophils is enhanced by atrial natriuretic factor. Two inhibitors of soluble guanylate cyclase, 6-anilino-5,8-quinolinedione (LY 83583) and methylene blue, have no effect on stimulation of migration by atrial natriuretic factor. Atrial natriuretic factor-activated migration is inhibited by pertussis toxin. Migration by electroporated neutrophils is synergistically enhanced by guanosine-5'-[gamma thio]triphosphate (GTP gamma[S]) and atrial natriuretic factor or by GTP gamma[S] and chemotactic peptide, while GTP gamma[S] and dioctanoyl glycerol give an additive effect. The results suggest that besides a modulation via cGMP a part of the effect of atrial natriuretic factor on migration is regulated via the ANF receptor-subtype that does not activate guanylate cyclase.