Human mast cells express two leukotriene C(4) synthase isoenzymes and the CysLT(1) receptor.
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 LTC(4), the parent compound of cys-LTs, is catalyzed by a specific GSH transferase termed LTC(4) 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 C(4), i.e., microsomal GSH transferase type 2. Furthermore, these cells abundantly express CysLT(1) receptors that are mostly located at the surface of both types of mast cells, as judged by immunohistochemistry. In addition, stimulation of CBMC with LTC(4) and LTD(4) elicits an immediate and dose-dependent (10(-7)-10(-11) M) mobilization of intracellular Ca(2+), which can be blocked with specific CysLT(1) 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 CysLT(1) suggests that these lipid mediators may be involved in autocrine signaling pathways regulating mast cell functions.
Sjöström
Mattias
M
Department of Medical Biochemistry and Biophysics, Division of Chemistry II, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Jakobsson
Per Johan
PJ
Juremalm
Mikael
M
Ahmed
Ahmed
A
Nilsson
Gunnar
G
Macchia
Luigi
L
Haeggström
Jesper Z
JZ
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008407:Mast Cells / Q000201:enzymology / Q000378:metabolism*; D008565:Membrane Proteins; D012333:RNA, Messenger / Q000235:genetics; D018077:Receptors, Leukotriene / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018411:Spodoptera
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; C412375:cysteinyl leukotriene receptor 2; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; C083169:leukotriene D4 receptor