Inhibitory Activities of Compounds from the Marine Actinomycete Williamsia sp. MCCC 1A11233 Variant on IgE-Mediated Mast Cells and Passive Cutaneous Anaphylaxis.

Abstract

The compounds of the deep-sea-derived marine Williamsia sp. MCCC 1A11233 (CDMW) were isolated, which are secondary metabolites of the actinomycetes. In this study, seven kinds of CDMW were found to decrease degranulation and histamine release in immunoglobulin E (IgE)-mediated rat basophilic leukemia (RBL)-2H3 cells. The production of cytokines (tumor necrosis factor-α, interleukin-4) was inhibited by these CDMW in RBL-2H3 cells, and their chemical structures were established mainly based on detailed analysis of their NMR spectra. CDMW-3, CDMW-5, and CDMW-15 were further demonstrated to block mast cell-dependent passive cutaneous anaphylaxis in IgE-sensitized mice. Bone marrow mononuclear cells (BMMCs) were established to clarify the effect of CDMW-3, CDMW-5, and CDMW-15 on mast cells. The seven kinds of CDMW decreased the degranulation and histamine release of BMMCs. Furthermore, flow cytometry results indicated that CDMW-3, CDMW-5, and CDMW-15 increased the annexin+ cell population of BMMCs. In conclusion, CDMW-3, CDMW-5, and CDMW-15 have obvious antiallergic activity due to induction of the apoptosis of mast cells.