MECHANISMS OF PROPIONIBACTERIUM ACNES MEDIATED INFLAMMATION IN THE SKIN DISEASE, ACNE VULGARIS

The interaction of Propionibacterium acnes and human host defense systems was studied in order to shed light on the mechanisms of inflammation in acne vulgaris. P. acnes cells were shown to activate the classical and alternative pathways of human complement in a dose-dependent manner. The ability of P. acnes strains to activate the classical pathway was proportional to the antibody titer of the serum source. Acne lesion contents also activated complement; and this activation was stimulated by the presence of anti-P. acnes antibodies in the serum. Complement activation by P. acnes cells resulted in the production of C5-derived neutrophil chemotactic activity. P. acnes' ability to activate the alternative pathway of complement was shown to be due to a cell wall carbohydrate which was sensitive to extraction with trichloracetic acid, formamide and periodate. The extracted carbohydrate was not capable of inducing C3-9 consumption, but would selectively deplete alternative pathway reactivity from human serum. P. acnes was also shown to produce a low molecular weight neutrophil chemotactic factor as a metabolic by-product. The production of chemotactic factor was decreased by growth of P. acnes in sub-minimal inhibitory concentrations of tetracycline, erythromycin and minocycline. Incubation of P. acnes, neutrophils and serum resulted in the release of lysosomal hydrolases without causing the death of the neutrophils. This release was found to be dependent on the presence of anti-P. acnes antibodies in the serum. The results are discussed in relation to the pathogenesis of inflammatory acne vulgaris, therapy of acne vulgaris, activation of the alternative pathway of complement, and activation of macrophages.