Lianos E A, Bresnahan B A, Pan C
Medical College of Wisconsin, Department of Medicine, Milwaukee 53226.
J Clin Invest. 1991 Aug;88(2):623-31. doi: 10.1172/JCI115347.
The synthesis, cell origin, and physiologic role of eicosanoids were investigated in a model of mesangial cell immune injury induced by a monoclonal antibody against the rat thymocyte antigen Thy 1.1 also expressed in rat mesangial cells. A single intravenous injection of the antibody resulted in enhanced glomerular synthesis of thromboxane (Tx)B2, leukotriene (LT)B4, and 12-hydroxyeicosatetraenoic acid (HETE), whereas that of PGE2 and PGF2 alpha was either unaltered or impaired. The enhanced eicosanoid synthesis was associated with decrements in glomerular filtration rate (GFR) and renal blood flow (RBF). Complement activation mediated both the increments in TxB2, LTB4, and 12-HETE and the decrements in GFR and RBF. The decrements in GFR were abolished by the TxA2 receptor antagonist SQ-29,548. Although both neutrophiles and Ia (+) leukocytes infiltrated glomeruli, glomerular LTB4 originated mainly from the latter. Platelets entirely accounted for the enhanced 12-HETE synthesis in isolated glomeruli and to a lesser extent for that of LTB4 and TxB2. Glomerular PGE2 and PGF2 alpha originated from mesangial cells as their impaired synthesis coincided with extensive mesangial cell lysis. The observations indicate that in mesangial cell immune injury vasoactive and proinflammatory eicosanoids originate from recruited or activated Ia (+) leukocytes and platelets and may exert paracrine effects on mesangial cells.
在由一种针对大鼠系膜细胞中也表达的大鼠胸腺细胞抗原Thy 1.1的单克隆抗体诱导的系膜细胞免疫损伤模型中，对类花生酸的合成、细胞起源及生理作用进行了研究。单次静脉注射该抗体导致肾小球血栓素（Tx）B2、白三烯（LT）B4和12-羟基二十碳四烯酸（HETE）的合成增强，而前列腺素E2（PGE2）和前列腺素F2α（PGF2α）的合成要么未改变，要么受损。类花生酸合成增强与肾小球滤过率（GFR）和肾血流量（RBF）的降低相关。补体激活介导了TxB2、LTB4和12-HETE的增加以及GFR和RBF的降低。TxA2受体拮抗剂SQ-29548消除了GFR的降低。尽管中性粒细胞和Ia（+）白细胞都浸润了肾小球，但肾小球LTB4主要来源于后者。血小板完全导致了分离肾小球中12-HETE合成的增强，对LTB4和TxB2合成的影响较小。肾小球PGE2和PGFα起源于系膜细胞，因为它们合成受损与广泛的系膜细胞溶解同时发生。这些观察结果表明，在系膜细胞免疫损伤中，血管活性和促炎性类花生酸起源于募集或激活的Ia（+）白细胞和血小板，并可能对系膜细胞发挥旁分泌作用。
