Influence of IgE-mediated activation of cultured human mast cells on proliferation and type I collagen production by human dermal fibroblasts.

Abstract

Mast cells have been suggested to be involved in fibrotic conditions, but it still remains unknown whether IgE-mediated activation of human mast cells promotes fibrogenesis by human fibroblasts. The purpose of this study was to determine whether IgE-mediated activation of cultured human mast cells can promote fibrogenesis by cultured human dermal fibroblasts. Mast cells derived from human umbilical cord blood cells were incubated with IgE and then activated by anti-IgE, and histamine release was measured. IgE-sensitized mast cells were cocultured with fibroblasts from normal dermis and activated with anti-IgE to induce histamine release, after which proliferation and type I collagen synthesis by the fibroblasts were determined. Coculture of subconfluent human dermal fibroblasts with IgE-sensitized mast cells did not affect fibroblast proliferation. However, fibroblast proliferation was increased by activated mast cells, and a significant increase was observed in the presence of 10(5) or 3 x 10(5) mast cells/mL. The promotion of fibroblast proliferation by mast cells (3 x 10(5)/mL) was partly inhibited by ketotifen at a concentration that significantly reduced histamine release from mast cells. On the other hand, IgE-mediated activation of mast cells did not increase type I collagen production by confluent human dermal fibroblasts. IgE-mediated activation of cultured human mast cells could increase the proliferation of human dermal fibroblasts, but did not promote type I collagen production by the fibroblasts under the conditions tested.