Group IID heparin-binding secretory phospholipase A(2) is expressed in human colon carcinoma cells and human mast cells and up-regulated in mouse inflammatory tissues.
Group IID secretory phospholipase A(2) (sPLA(2)-IID), a heparin-binding sPLA(2) that is closely related to sPLA(2)-IIA, augments stimulus-induced cellular arachidonate release in a manner similar to sPLA(2)-IIA. Here we identified the residues of sPLA(2)-IID that are responsible for heparanoid binding, are and therefore essential for cellular function. Mutating four cationic residues in the C-terminal portion of sPLA(2)-IID resulted in abolition of its ability to associate with cell surface heparan sulfate and to enhance stimulus-induced delayed arachidonate release, cyclooxygenase-2 induction, and prostaglandin generation in 293 cell transfectants. As compared with several other group II subfamily sPLA(2)s, which were equally active on A23187- and IL-1-primed cellular membranes, sPLA(2)-IID showed apparent preference for A23187-primed membranes. Several human colon carcinoma cell lines expressed sPLA(2)-IID and sPLA(2)-X constitutively, the former of which was negatively regulated by IL-1. sPLA(2)-IID, but not other sPLA(2) isozymes, was expressed in human cord blood-derived mast cells. The expression of sPLA(2)-IID was significantly altered in several tissues of mice with experimental inflammation. These results indicate that sPLA(2)-IID may be involved in inflammation in cell- and tissue-specific manners under particular conditions.
Murakami
Makoto
M
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan. mako@pharm.showa-u.ac.jp
Yoshihara
Kumiko
K
Shimbara
Satoko
S
Sawada
Masatsugu
M
Inagaki
Naoki
N
Nagai
Hiroichi
H
Naito
Mikihiko
M
Tsuruo
Takashi
T
Moon
Tae Churl
TC
Chang
Hyeun Wook
HW
Kudo
Ichiro
I
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism*; D015854:Up-Regulation
D016718:Arachidonic Acid; D010741:Phospholipases A