Mesangial cell immune injury. Synthesis, origin, and role of eicosanoids. J Clin Invest 1991 Aug;88(2):623-31
Date
08/01/1991Pubmed ID
1677947Pubmed Central ID
PMC295400DOI
10.1172/JCI115347Scopus ID
2-s2.0-0025894978 (requires institutional sign-in at Scopus site) 51 CitationsAbstract
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.
Author List
Lianos EA, Bresnahan BA, Pan CAuthors
Barbara A. Bresnahan MD Professor in the Medicine department at Medical College of WisconsinCynthia G. Pan MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAnimals
Antibodies, Monoclonal
Antigens, Surface
Eicosanoids
Glomerular Filtration Rate
Glomerular Mesangium
Hydroxyeicosatetraenoic Acids
Leukocytes
Leukotriene B4
Male
Mice
Prostaglandins
Rats
Rats, Inbred Strains
Renal Circulation
Thromboxane B2
Thy-1 Antigens
