Temporal infiltration of leukocyte subsets into mouse skin inflamed with phorbol ester.

Abstract

We have previously shown that multiple topical applications, over 11 days, of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a persistent inflammatory reaction characterized by edema, cell infiltration and epidermal hyperplasia. In order to characterize the cell infiltrate during the establishment of this inflammatory reaction, immunohistochemistry was performed using two monoclonal antibodies: MOMA-2, a macrophage antibody and Thy-1, a pan T-cell antibody. The level of polymorphonuclear leukocytes (PMNs) peaked by day 3 at 160-fold over nontreated controls and then subsided to a 30-fold elevation on days 7-10. By day 4, the number of macrophages increased 2.9-fold over the nontreated control and by day 10 were elevated 6.0-fold over the nontreated control. In comparison, the number of T-cells present by day 7 was significantly elevated 9.5-fold over the nontreated group and peaked at day 8 with a 19-fold elevation relative to nontreated controls. Topical treatment of animals with hydrocortisone valerate resulted in a dramatic (> 60%) reduction in the number of T-cells present in the tissue. In contrast, there was no effect of the steroid on the number of macrophages present in the tissue. The identification of specific cell types and their time course of infiltration is consistent with the development of a chronic inflammatory lesion.