Sapirstein A, Bonventre J V
Department of Anesthesiology and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Biochim Biophys Acta. 2000 Oct 31;1488(1-2):139-48. doi: 10.1016/s1388-1981(00)00116-5.
The cytosolic 85 kDa phospholipase A(2) (cPLA(2)) is a unique member of the phospholipase A(2) (PLA(2)) superfamily. Because PLA(2) activity and eicosanoid production are important in normal and pathophysiological states we and the laboratory of Shimizu created a mouse deficient in cPLA(2) (cPLA(2)(-/-) mouse). cPLA(2)(-/-) mice develop normally but the females have severe reproductive defects. cPLA(2)(-/-) mice suffer smaller infarcts and fewer neurological deficits after transient occlusion of the middle cerebral artery and have less injury after administration of a dopaminergic selective neurotoxin. cPLA(2)(-/-) mice have a more rapid recovery from allergen-induced bronchoconstriction and have no airway hyperresponsiveness. Peritoneal macrophages from cPLA(2)(-/-) mice fail to produce prostaglandins, leukotriene B(4) and cysteinyl leukotrienes after stimulation. Bone marrow-derived mast cells from cPLA(2)(-/-) mice fail to produce eicosanoids in either immediate or delayed phase responses. Thus the cPLA(2) knockout mouse has revealed important roles of cPLA(2) in normal fertility, generation of eicosanoids from inflammatory cells, brain injuries and allergic responses. Furthermore the cPLA(2)(-/-) mouse reveals that the many other forms of PLA(2) cannot replace many functions of cPLA(2). The importance of cPLA(2) in inflammation and tissue injury suggests that pharmacological targeting of this enzyme may have important therapeutic benefits.
胞质85 kDa磷脂酶A2（cPLA2）是磷脂酶A2（PLA2）超家族中的一个独特成员。由于PLA2活性和类花生酸生成在正常及病理生理状态中都很重要，我们和清水实验室培育出了一种cPLA2基因缺失的小鼠（cPLA2-/-小鼠）。cPLA2-/-小鼠发育正常，但雌性小鼠存在严重的生殖缺陷。短暂性大脑中动脉闭塞后，cPLA2-/-小鼠的梗死灶较小，神经功能缺损较少，并且在给予多巴胺能选择性神经毒素后损伤也较小。cPLA2-/-小鼠从变应原诱导的支气管收缩中恢复得更快，且没有气道高反应性。cPLA2-/-小鼠的腹腔巨噬细胞在受到刺激后无法产生前列腺素、白三烯B4和半胱氨酰白三烯。cPLA2-/-小鼠骨髓来源的肥大细胞在即时或延迟期反应中均无法产生类花生酸。因此，cPLA2基因敲除小鼠揭示了cPLA2在正常生育、炎症细胞产生类花生酸、脑损伤和过敏反应中的重要作用。此外，cPLA2-/-小鼠还表明，许多其他形式的PLA2无法替代cPLA2的多种功能。cPLA2在炎症和组织损伤中的重要性表明，对该酶进行药物靶向治疗可能具有重要的治疗益处。
