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

A potent, heat-labile leukotoxic material was extracted from Actinobacillus 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 evidence to be presented suggests that the cell membrane of the monocyte may be the primary target in the development of these phenomena. Previous studies have shown that Y4 toxin also kills human polymorphonuclear leukocytes but not other cell types. It is conceivable that disruption of polymorphonuclear leukocytes and monocytes by Y4 toxin in the gingival crevice area may be relevant in the pathogenesis of juvenile periodontitis.