Biochemical and morphological characterization of the killing of human monocytes by a leukotoxin derived from Actinobacillus actinomycetemcomitans

Abstract

A potent, heat-labile leukotoxic material was extracted from A. actinomycetemcomitans (strain Y4), an anaerobic gram-negative microorganism originally isolated from subgingival plaque in a patient with juvenile periodontitis. The cytopathic effects of Y4 toxin on purified monocytes were studied by the extracellular release of radioactive cytoplasmic markers and cell enzymes and by time-lapse microcinematography. Y4 toxin rapidly bound to the cells, producing dose- and time-dependent alterations culminating in cell death and release of intracellular constituents into the culture medium. The cell membrane of the monocyte may be the primary target in the development of these phenomena. Y4 toxin kills human polymorphonuclear leukocytes [PMN] but not other cell types. Disruption of PMN and monocytes by Y4 toxin in the gingival crevice area may be relevant in the pathogenesis of juvenile periodontitis.