Boilard Eric, Bourgoin Sylvain G, Bernatchez Chantale, Poubelle Patrice E, Surette Marc E
Pilot Therapeutics Inc., 2000 Daniel Island Dr., Suite 440, Charleston, SC 29492, USA.
FASEB J. 2003 Jun;17(9):1068-80. doi: 10.1096/fj.02-0938com.
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.
人IIA组磷脂酶A2（hIIA PLA2）是一种与炎症性疾病相关的14 kDa分泌酶。hIIA PLA2的一个新发现特性是对硫酸乙酰肝素蛋白聚糖（HSPG）磷脂酰肌醇蛋白聚糖-1具有结合亲和力。在本研究中，对hIIA PLA2与凋亡人T细胞的结合进行了研究。很少或没有外源性hIIA PLA2与CD3激活的T细胞结合，但在经抗CD95诱导发生凋亡的激活T细胞上检测到显著结合。与早期凋亡T细胞的结合大于晚期凋亡细胞。加入肝素以及用肝素酶III水解HSPG仅部分抑制hIIA PLA2与凋亡细胞的结合，表明其与HSPG和其他结合蛋白存在相互作用。两种低分子量HSPG与hIIA PLA2从凋亡T细胞中共免疫沉淀，但未从活细胞中沉淀。用hIIA PLA2处理CD95刺激的T细胞导致细胞释放花生四烯酸而非油酸，且这种释放被肝素和肝素酶III阻断。总之，这些结果表明hIIA PLA2通过与HSPG相互作用在凋亡细胞花生四烯酸释放中发挥作用及其在炎症性疾病进展中的潜在意义。
