Cytosolic Acidification as an Early Transductory Signal of Human Neutrophil Chemotaxis

Abstract

The inflammatory reaction of human neutrophils consists of two successive phases. In the first, designated chemotaxis, the cells home in on a foreign intruder. In the second, the cells attempt to eliminate the intruder by secreting lysosomal enzymes and superoxide anions. The initiation of chemotaxis involves prompt morphological changes that are manifested by a sharp biphasic drop in light scattering, accompanied by a transient cytosolic acidification. In a search for a causal relation between these two events, the neutrophil cytoplasm was abruptly acidified by the application of sodium propionate. This evoked a pulse of decreasing light-scattering, the time course and amplitude of which were practically identical to the rapid response induced by chemoattractants such as N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). Both fMLP- and sodium propionate-induced responses were unaffected by amiloride, but were inhibited with a similar dose-dependence by a series of proton uncouplers. The initial phase of the cytosolic acidification seems, therefore, to fulfill the criteria for a second messenger for the initiation of chemotaxis.