Effects of PGE2 and a thromboxane A2 analogue on uptake of IgG complexes and LDL by mesangial cells.
Vasoactive agents such as angiotensin (ANG) and eicosanoids can influence macromolecular deposition in the glomerular mesangium. We studied whether prostaglandin E2 (PGE2) and U-46619 (a stable analogue of thromboxane A2) could directly affect the uptake of immunoglobulin G (IgG) complexes or low-density lipoprotein (LDL) by cultured rat mesangial cells (MC). Preincubation of MC with PGE2 (10(-6) M) resulted in decreased uptake (in counts.min-1.well-1) of IgG complexes (PGE2, 2,589 +/- 72; control, 3,840 +/- 114; P less than 0.001) and LDL particles (PGE2, 23,176 +/- 1,145; control, 37,216 +/- 4,520; P less than 0.05). MC preincubated with forskolin (10(-5) M) also showed decreased uptake of IgG complexes (forskolin, 2,896 +/- 196; control, 3,840 +/- 114; P less than 0.005) and LDL particles (forskolin, 23,176 +/- 1,145; control, 37,216 +/- 4,520; P less than 0.05). In contrast, preincubation with ANG II (5 x 10(-7) M) showed significantly higher uptake of IgG complexes (ANG II, 4,475 +/- 282; control, 3,787 +/- 277; P less than 0.05) and LDL (ANG II, 48,573 +/- 1,079; control, 44,697 +/- 770; P less than 0.05). Similarly, preincubation with U-46619 (10(-6) M) resulted in significantly higher uptake of IgG complexes (U-46619, 5,370 +/- 300; control, 3,659 +/- 307; P less than 0.02) and LDL (U-46619, 48,298 +/- 1,418; control, 44,697 +/- 770; P less than 0.05). After preincubation with cyclooxygenase inhibitor meclofenamate (10(-6) M), ANG II (5 x 10(-7) M) resulted in a significantly higher uptake of IgG complexes compared with uptake by MC treated with ANG II alone (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Singhal
P C
PC
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Gupta
S
S
Shen
Z
Z
Schlondorff
D
D
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000199:Actins / Q000032:analysis; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D051381:Rats; D013928:Thromboxane A2 / Q000031:analogs & derivatives
D000199:Actins; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D011450:Prostaglandin Endoperoxides, Synthetic; D005576:Colforsin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine