Mast cell-dependent amplification of an immunologically nonspecific inflammatory response. Mast cells are required for the full expression of cutaneous acute inflammation induced by phorbol 12-myristate 13-acetate

Abstract

Mast cells clearly are critical for the expression of some IgE-dependent responses, but their roles in other forms of inflammation are uncertain. We previously described a new model system for defining the unique contribution of mast cells to biologic responses in vivo, genetically mast cell-deficient WBB6F1-W/Wv mice that have undergone selective local repair of their mast cell deficiency by the injection of IL-3-dependent cultured mast cells derived from the congenic normal (WBB6F1-+/+) mice. Using this approach, we analyzed the contribution of mast cells to the acute inflammation induced by the epicutaneous application of PMA. Even though PMA can activate a wide variety of cell types that may contribute to acute inflammation, we found that mast cells were required for the full expression of the tissue swelling and leukocyte infiltration associated with the response to the agent in vivo. Thus, in WBB6F1-W/Wv mice selectively reconstituted with dermal mast cells by intradermal injection of cultured WBB6F1-+/+ mast cells into the left ear only, PMA induced approximately twice the tissue swelling and neutrophil infiltration in the mast cell-reconstituted left ears as in the contralateral control ears. This represents the first use of W/Wv mice locally reconstituted with mast cells to confirm the hypothesis that mast cells can represent an important amplification mechanism in acute inflammatory responses of nonimmunologic origin. It also defines a model system that may be generally useful for investigating mast cell-dependent and -independent aspects of acute inflammatory responses.