The Journal of Immunology, Vol 138, Issue 11 3758-3765, Copyright © 1987 by American Association of Immunologists

ARTICLES

Complement dependence of antibody-induced mesangial cell injury in the rat

T Yamamoto and CB Wilson

Intravenous administration of rabbit anti-rat thymocyte serum (ATS) reactive with Thy-1-like antigens present on rat mesangial cells induces almost immediate (1-hr) mesangial cell injury in rats followed by sequential mesangiolytic and mesangial-proliferative/infiltrative lesions. To determine the role of complement in these ATS-induced glomerular lesions, ATS was given to Lewis rats that had been depleted of C3 by cobra venom factor (CVF). CVF treatment prevented the degenerative changes in mesangial cells and accumulation of even the few polymorphonuclear leukocytes (PMN) seen in the glomeruli (2.67 PMN/glomerulus) 1 hr after ATS-treatment in rats not given CVF. In addition, CVF prevented the mesangiolysis and mesangial hypercellularity seen at day 4. Rat C3 and late complement components identified in the mesangial of ATS-treated rats in close association with the deposition of rabbit immunoglobulin G was also absent as a result of CVF treatment. CVF treatment did not affect binding of ATS to glomeruli as studied by immunofluorescence or paired label radioisotope techniques. The depletion of leukocytes and/or PMN by irradiation or treatment with anti-I-MN serum had no effect on the induction of the acute mesangial cell damage or the mesangiolytic lesion. Irradiation did diminish the 4-day proliferative/infiltrative lesion. Complement depletion normalized the ATS-induced increase in mesangial uptake of heat-aggregated human gamma-globulin (655.0 +/- 35.2 micrograms in ATS- treated vs 20.3 +/- 2.9 micrograms/5 X 10(4) glomeruli in ATS plus CVF- treated rats; mean +/- SEM). Small immune deposits present in the mesangial areas of kidneys 4 to 5 days after CVF treatment represented CVF-anti-CVF antibody-C3 complexes. The model of mesangial cell damage induced by ATS in the rat is complement-dependent and may relate, at least in part, to complement-mediated mesangial cell lysis.

This article has been cited by other articles:

				Y. Kawasaki, M. Tanji, K. Takano, Y. Fukuda, M. Isome, R. Nozawa, H. Suzuki, and M. Hosoya The leukotriene B4 receptor antagonist ONO-4057 inhibits mesangioproliferative changes in anti-Thy-1 nephritis Nephrol. Dial. Transplant., December 1, 2005; 20(12): 2697 - 2703. [Abstract] [Full Text] [PDF]

				H. Takahara, I. Shirato, K. Asanuma, M. Yamashita, Y. Takeda, and Y. Tomino Tensin Is Expressed in Glomerular Mesangial Cells and Is Related to Their Attachment to Surrounding Extracellular Matrix J. Histochem. Cytochem., May 1, 2004; 52(5): 683 - 692. [Abstract] [Full Text] [PDF]

				R. J. Quigg Complement and the Kidney J. Immunol., October 1, 2003; 171(7): 3319 - 3324. [Full Text] [PDF]

				S. ISHIZUKA, R. CUNARD, S. POUCELL-HATTON, L. WEAD, M. LORTIE, S. C. THOMSON, F. B. GABBAI, J. SATRIANO, and R. C. BLANTZ Agmatine Inhibits Cell Proliferation and Improves Renal Function in Anti--Thy-1 Glomerulonephritis J. Am. Soc. Nephrol., December 1, 2000; 11(12): 2256 - 2264. [Abstract] [Full Text]

				K. Kobayashi, F. Sano, M. Mutai, and J. Sugimoto Glomerulonephritis with Fibrillary Deposition in a Transgenic Mouse Carrying the Human Prototype c-Ha-ras Gene (rasH2 Mouse) Toxicol Pathol, March 1, 2000; 28(2): 359 - 362. [Abstract] [PDF]

				R. Westerhuis, S. C. van Straaten, M. G. A. van Dixhoorn, N. van Rooijen, N. A. M. Verhagen, C. D. Dijkstra, E. de Heer, and M. R. Daha Distinctive Roles of Neutrophils and Monocytes in Anti-Thy-1 Nephritis Am. J. Pathol., January 1, 2000; 156(1): 303 - 310. [Abstract] [Full Text] [PDF]

				T. SATO, M. G. A. VAN DIXHOORN, F. A. PRINS, A. MOONEY, N. VERHAGEN, Y. MUIZERT, J. SAVILL, L. A. VAN ES, and M. R. DAHA The Terminal Sequence of Complement Plays an Essential Role in Antibody-Mediated Renal Cell Apoptosis J. Am. Soc. Nephrol., June 1, 1999; 10(6): 1242 - 1252. [Abstract] [Full Text]

				H. Trachtman Effects of Chemically Modified Tetracyclines on iNOS in Mesangial Cells: Impact on Experimental Glomerulonephritis Advances in Dental Research, November 1, 1998; 12(1): 123 - 125. [PDF]

				R. J. Quigg, C. He, A. Lim, D. Berthiaume, J. J. Alexander, D. Kraus, and V. Michael Holers Transgenic Mice Overexpressing the Complement Inhibitor Crry as a Soluble Protein Are Protected from Antibody-induced Glomerular Injury J. Exp. Med., October 5, 1998; 188(7): 1321 - 1331. [Abstract] [Full Text] [PDF]