The biologic activity of mast cell granules. VI. The effect of vinblastine-induced neutropenia on rat cutaneous late phase reactions.

Abstract

Type I immediate hypersensitivity reactions in human and rat skin may be followed by late phase reactions (LPR). A consistent feature of both human and rat LPR is the early histologic appearance of neutrophils, which, in rats, is followed by the later appearance (8 to 24 hr) of mononuclear cells. To determine the importance of the neutrophil in the development of LPR, rats were depleted of neutrophils using parenteral injections of vinblastine sulfate (VS). VS produced a dose-dependent neutropenia, with the maximal effect on day 4. LPR that were induced with anti-IgE, isolated mast cell granules (MCG), or purified high (greater than 10,000 daltons) and low (500 to 10,000 daltons) m.w. fractions obtained from MCG were significantly abrogated in VS-treated rats. In neutropenic rats previously immunized with complete Freund's adjuvant, the intensity of inflammatory reactions produced by skin testing with purified protein derivatives was also significantly reduced. Administration of exogenous neutrophils to neutropenic animals partially reconstituted the reduced LPR. These data confirm and extend previous observations on the contribution of neutrophils to delayed hypersensitivity reactions and provide evidence that the neutrophil is critical for the development of rat cutaneous LPR as well.