Mouse group X secretory phospholipase A2 induces a potent release of arachidonic acid from spleen cells and acts as a ligand for the phospholipase A2 receptor.
Group X secretory phospholipase A2 (sPLA2-X) has recently been shown to possess a powerful potency for releasing arachidonic acid from cell membrane phospholipids. Here, we report the purification of mouse pro- and mature forms of sPLA2-X, as well as its expression and biological functions. Purified pro-sPLA2-X was found to possess a propeptide of 11 amino acid residues attached at the NH2-terminals of the mature protein, and showed as little as 8% of the PLA2 activity of the mature form. Limited proteolysis of pro-sPLA2-X with trypsin resulted in the appearance of the mature form with a concomitant increase in PLA2 activity, suggesting a requirement of proteolytic removal of the propeptide for the optimal activity. The expression of sPLA2-X mRNA was detected in various tissues including the lung, thymus, and spleen, and immunohistochemical analysis revealed its expression in splenic macrophages. In the spleen cells, mature sPLA2-X elicited a prompt release of arachidonic acid with significant production of prostaglandin E2 more efficiently than group IB and IIA sPLA2s. In addition, sPLA2-X was identified as a high-affinity ligand for both native and recombinant form of mouse PLA2 receptor (PLA2R). However, there was no significant difference in the sPLA2-X-induced arachidonic acid release responses in the spleen cells between wild-type and PLA2R-deficient mice. These findings strongly suggest that sPLA2-X possesses two distinct biological functions in mice: it elicits a marked release of arachidonic acid from membrane phospholipids leading to the production of lipid mediators based on its enzymatic potency, and it acts as a natural ligand for the PLA2R that has been shown to play a critical role in the production of inflammatory cytokines during endotoxic shock.
Morioka
Y
Y
Shionogi Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan.
Saiga
A
A
Yokota
Y
Y
Suzuki
N
N
Ikeda
M
M
Ono
T
T
Nakano
K
K
Fujii
N
N
Ishizaki
J
J
Arita
H
H
Hanasaki
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D005260:Female; D054501:Group II Phospholipases A2; D054509:Group X Phospholipases A2; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D054507:Receptors, Phospholipase A2; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000378:metabolism*; D014018:Tissue Distribution
D004792:Enzyme Precursors; D008024:Ligands; C516357:Pla2r1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D011994:Recombinant Proteins; D016718:Arachidonic Acid; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054509:Group X Phospholipases A2; D054467:Phospholipases A2; C516366:Pla2g10 protein, mouse