Human mast cells express two leukotriene C4 synthase isoenzymes and the CysLT1 receptor |
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Authors: | Mattias Sjöström Per-Johan Jakobsson Mikael Juremalm Ahmed Ahmed Gunnar Nilsson Luigi Macchia Jesper Z Haeggström |
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Institution: | 1. Department of Medical Biochemistry and Biophysics, Division of Chemistry II, Karolinska Institutet, S-171 77 Stockholm, Sweden;2. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, S-751 85, Uppsala, Sweden;3. Department of Clinical Immunology and Allergology, University of Bari, 70124 Bari, Italy |
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Abstract: | Cysteinyl-leukotrienes (cys-LTs) are potent smooth muscle contracting agents, especially in the respiratory tract and microcirculation, and play a key role in inflammatory and allergic diseases. The final step in the biosynthesis of LTC4, the parent compound of cys-LTs, is catalyzed by a specific GSH transferase termed LTC4 synthase, which is typically expressed in certain bone marrow-derived cells such as eosinophils and mast cells.Here we report that the human mast cell line HMC-1 as well as human mast cells derived from cord blood (CBMC) express a second enzyme capable of synthesizing leukotriene C4, i.e., microsomal GSH transferase type 2. Furthermore, these cells abundantly express CysLT1 receptors that are mostly located at the surface of both types of mast cells, as judged by immunohistochemistry. In addition, stimulation of CBMC with LTC4 and LTD4 elicits an immediate and dose-dependent (10?7–10?11 M) mobilization of intracellular Ca2+, which can be blocked with specific CysLT1 receptor antagonists. Taken together, our data suggest that human mast cells are equipped with two enzymes that can catalyze the committed step in the biosynthesis of cys-LTs. Moreover, the expression of the cognate receptor CysLT1 suggests that these lipid mediators may be involved in autocrine signaling pathways regulating mast cell functions. |
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Keywords: | Human Mast cell Inflammation Lipid mediator Molecular Biology |
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