Interaction of low molecular weight group IIA phospholipase A2 with apoptotic human T cells: role of heparan sulfate proteoglycans.
Human group IIA phospholipase A2 (hIIA PLA2) is a 14 kDa secreted enzyme associated with inflammatory diseases. A newly discovered property of hIIA PLA2 is the binding affinity for the heparan sulfate proteoglycan (HSPG) glypican-1. In this study, the binding of hIIA PLA2 to apoptotic human T cells was investigated. Little or no exogenous hIIA PLA2 bound to CD3-activated T cells but significant binding was measured on activated T cells induced to undergo apoptosis by anti-CD95. Binding to early apoptotic T cells was greater than to late apoptotic cells. The addition of heparin and the hydrolysis of HSPG by heparinase III only partially inhibited hIIA PLA2 binding to apoptotic cells, suggesting an interaction with both HSPG and other binding protein(s). Two low molecular weight HSPG were coimmunoprecipitated with hIIA PLA2 from apoptotic T cells, but not from living cells. Treatment of CD95-stimulated T cells with hIIA PLA2 resulted in the release of arachidonic acid but not oleic acid from cells and this release was blocked by heparin and heparinase III. Altogether, these results suggest a role for hIIA PLA2 in the release of arachidonic acid from apoptotic cells through interactions with HSPG and its potential implication in the progression of inflammatory diseases.
Boilard
Eric
E
Pilot Therapeutics Inc., 2000 Daniel Island Dr., Suite 440, Charleston, SC 29492, USA. MarcS@pilott.com
Bourgoin
Sylvain G
SG
Bernatchez
Chantale
C
Poubelle
Patrice E
PE
Surette
Marc E
ME
D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D054501:Group II Phospholipases A2; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D010718:Phosphatidylserines / Q000378:metabolism; D010741:Phospholipases A / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D054467:Phospholipases A2; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D054507:Receptors, Phospholipase A2; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D016718:Arachidonic Acid; D054501:Group II Phospholipases A2; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D010718:Phosphatidylserines; D010741:Phospholipases A; D054467:Phospholipases A2; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; C516360:PLA2R1 protein, human