【文章名】Inherited human cPLA(2 alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction
[摘要]：Cytosolic phospholipase A(2 alpha) (cPLA(2 alpha)) hydrolyzes arachidonic acid from cellular membrane phospholipids, thereby providing enzymatic substrates for the synthesis of eicosanoids, such as prostaglandins and leukotrienes. Considerable understanding of cPLA(2 alpha) function has been derived from investigations of the enzyme and from cPLA(2 alpha)-null mice, but knowledge of discrete roles for this enzyme in humans is limited. We investigated a patient hypothesized to have an inherited prostanoid biosynthesis deficiency due to his multiple, complicated small intestinal ulcers despite no use of cyclooxygenase inhibitors. Levels of thromboxane B-2 and 12-hydroxyeicosatetraenoic acid produced by platelets and leukotriene B-4 released from calcium ionophore-activated blood were markedly reduced, indicating defective enzymatic release of the arachidonic acid substrate for the corresponding cyclooxygenase and lipoxygenases. Platelet aggregation and degranulation induced by adenosine diphosphate or collagen were diminished but were normal in response to arachidonic acid. Two heterozygous single base pair mutations and a known SNP were found in the coding regions of the patient's cPLA(2 alpha) genes (p.[Ser111Pro]+[Arg485His; Lys651Arg]). The total PLA(2) activity in sonicated platelets was diminished, and the urinary metabolites of prostacyclin, prostaglandin E-2, prostaglandin D-2, and thromboxane A(2) were also reduced. These findings characterize what we believe is a novel inherited deficiency of cPLA(2).
