Mesangial cell immune injury. Synthesis, origin, and role of eicosanoids.
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.
Medical College of Wisconsin, Department of Medicine, Milwaukee 53226.
E A
EA
Lianos
B A
BA
Bresnahan
C
C
Pan
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D015777:Eicosanoids / Q000096:biosynthesis*; D005919:Glomerular Filtration Rate; D005920:Glomerular Mesangium / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007962:Leukocytes; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D013929:Thromboxane B2 / Q000096:biosynthesis; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D011453:Prostaglandins; D018800:Thy-1 Antigens; D007975:Leukotriene B4; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid