Cytosolic phospholipase A2 (cPLA2) plays a critical role in mast-cell-related allergic responses [Uozumi, Kume, Nagase, Nakatani, Ishii, Tashiro, Komagata, Maki, Ikuta, Ouchi et al. (1997) Nature (London) 390, 618–622]. Bone-marrow-derived mast cells from mice lacking cPLA2 (cPLA-/- mice) were used in order to better define the role of cPLA2 in the maturation and degranulation of such cells. Cross-linking of high-affinity receptors for IgE (FcεRI) on cells from cPLA-/-mice led to the release of negligible amounts of arachidonic acid or its metabolites, the cysteinyl leukotrienes and prostaglandin D2, indicating an essential role for cPLA2 in the production of these allergic and pro-inflammatory lipid mediators. In addition, the histamine content of the mast cells and its release from the cells were reduced to 60%. While these results are in agreement with a reduced anaphylactic phenotype of cPLA-/- mice, the ratios of release of histamine and β-hexosaminidase were, paradoxically, significantly higher for cells from cPLA-/- mice than for those from wild-type mice. Consistently, IgE-induced calcium influx in mast cells was greater and more prolonged in cells from cPLA-/- mice than in those from wild-type mice. Thus the loss of cPLA2 not only diminishes the release of lipid mediators, but also alters degranulation. While the overall effect is still a decrease in the release of mast cell mediators, explaining the in vivo findings, the present study proposes a novel link between cPLA2 and the degranulation machinery.
Skip Nav Destination
Article navigation
December 2000
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Research Article|
November 24 2000
Role of cytosolic phospholipase A2 in the production of lipid mediators and histamine release in mouse bone-marrow-derived mast cells
Noriaki NAKATANI;
Noriaki NAKATANI
1
*Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Search for other works by this author on:
Naonori UOZUMI;
Naonori UOZUMI
*Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Search for other works by this author on:
Kazuhiko KUME;
Kazuhiko KUME
*Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
Search for other works by this author on:
Makoto MURAKAMI;
Makoto MURAKAMI
†Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo 142-0064, Japan
Search for other works by this author on:
Ichiro KUDO;
Ichiro KUDO
†Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo 142-0064, Japan
Search for other works by this author on:
Takao SHIMIZU
Takao SHIMIZU
2
*Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
‡CREST of Japan Science and Technology Corporation, The University of Tokyo, Tokyo 113-0033, Japan
2To whom correspondence should be addressed (e-mail tshimizu@m.u-tokyo.ac.jp).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 15 2000
Revision Received:
August 07 2000
Accepted:
September 13 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 352 (2): 311–317.
Article history
Received:
May 15 2000
Revision Received:
August 07 2000
Accepted:
September 13 2000
Citation
Noriaki NAKATANI, Naonori UOZUMI, Kazuhiko KUME, Makoto MURAKAMI, Ichiro KUDO, Takao SHIMIZU; Role of cytosolic phospholipase A2 in the production of lipid mediators and histamine release in mouse bone-marrow-derived mast cells. Biochem J 1 December 2000; 352 (2): 311–317. doi: https://doi.org/10.1042/bj3520311
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.