This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Erwig, L.-P. Articles by Rees, A. J. Search for Related Content PubMed PubMed Citation Articles by Erwig, L.-P. Articles by Rees, A. J.

(American Journal of Pathology. 2000;156:295-301.)
© 2000 American Society for Investigative Pathology

Regular Articles

Macrophages from Inflamed but Not Normal Glomeruli Are Unresponsive to Anti-Inflammatory Cytokines

From the Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom

This study examined the properties and responsiveness to cytokines of macrophages purified from normal and nephritic glomeruli to ascertain whether macrophages activated in vivo develop programmed unresponsiveness to cytokines as do bone marrow-derived macrophages in vitro when activated by interferon- (IFN-), tumor necrosis factor (TNF), interleukin-4 (IL-4), or transforming growth factor-ß (TGF-ß). Macrophages from normal glomeruli did not generate nitric oxide (NO) spontaneously but only after treatment with IFN- and TNF-. NO generation by these macrophages was abrogated by administering IL-4, TGF-ß, or TNF- before but not after IFN- treatment. Glomerular macrophages also expressed ß-glucuronidase, which was increased by TGF-ß and decreased by IFN- and TNF. By contrast, glomerular macrophages from rats with nephrotoxic nephritis did not express ß-glucuronidase even after exposure to TGF-ß. Furthermore, they generated NO spontaneously, and this spontaneous generation of NO was not suppressed by IL-4, TGF-ß, or TNF-. Systemic treatment of nephritic rats with IL-4 reduced NO generation by 40% but did not prevent activation, which is similar to the effect of IL-4 on bone marrow-derived macrophages in vitro when given simultaneously with IFN-. We conclude that macrophages infiltrating inflamed glomeruli have developed programmed unresponsiveness to activating cytokines. This may enable them to function appropriately in the complex conditions within an inflammatory focus.

This article has been cited by other articles:

				Y. Wang, Y. Wang, Q. Cai, G. Zheng, V. W.S. Lee, D. Zheng, X. Li, T. K. Tan, and D. C.H. Harris By Homing to the Kidney, Activated Macrophages Potently Exacerbate Renal Injury Am. J. Pathol., June 1, 2008; 172(6): 1491 - 1499. [Abstract] [Full Text] [PDF]

				Y. Liu, K. N. Stewart, E. Bishop, C. J. Marek, D. C. Kluth, A. J. Rees, and H. M. Wilson Unique Expression of Suppressor of Cytokine Signaling 3 Is Essential for Classical Macrophage Activation in Rodents In Vitro and In Vivo J. Immunol., May 1, 2008; 180(9): 6270 - 6278. [Abstract] [Full Text] [PDF]

				H. M. Wilson, S. Chettibi, C. Jobin, D. Walbaum, A. J. Rees, and D. C. Kluth Inhibition of Macrophage Nuclear Factor-{kappa}B Leads to a Dominant Anti-Inflammatory Phenotype that Attenuates Glomerular Inflammation in Vivo Am. J. Pathol., July 1, 2005; 167(1): 27 - 37. [Abstract] [Full Text] [PDF]

				A. W. M. Minto, L.-P. Erwig, and A. J. Rees Heterogeneity of Macrophage Activation in Anti-Thy-1.1 Nephritis Am. J. Pathol., November 1, 2003; 163(5): 2033 - 2041. [Abstract] [Full Text] [PDF]

				L.-P. Erwig, D. C. Kluth, and A. J. Rees Macrophage heterogeneity in renal inflammation Nephrol. Dial. Transplant., October 1, 2003; 18(10): 1962 - 1965. [Full Text] [PDF]

				A. D. Dick, D. Carter, M. Robertson, C. Broderick, E. Hughes, J. V. Forrester, and J. Liversidge Control of myeloid activity during retinal inflammation J. Leukoc. Biol., August 1, 2003; 74(2): 161 - 166. [Abstract] [Full Text] [PDF]

				H.-J. Anders, M. Frink, Y. Linde, B. Banas, M. Wornle, C. D. Cohen, V. Vielhauer, P. J. Nelson, H.-J. Grone, and D. Schlondorff CC Chemokine Ligand 5/RANTES Chemokine Antagonists Aggravate Glomerulonephritis Despite Reduction of Glomerular Leukocyte Infiltration J. Immunol., June 1, 2003; 170(11): 5658 - 5666. [Abstract] [Full Text] [PDF]

				M. J. Robertson, L. P. Erwig, J. Liversidge, J. V. Forrester, A. J. Rees, and A. D. Dick Retinal Microenvironment Controls Resident and Infiltrating Macrophage Function during Uveoretinitis Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2250 - 2257. [Abstract] [Full Text] [PDF]

				D.-H. Kang, J. Kanellis, C. Hugo, L. Truong, S. Anderson, D. Kerjaschki, G. F. Schreiner, and R. J. Johnson Role of the Microvascular Endothelium in Progressive Renal Disease J. Am. Soc. Nephrol., March 1, 2002; 13(3): 806 - 816. [Abstract] [Full Text] [PDF]

				M. Hesse, M. Modolell, A. C. La Flamme, M. Schito, J. M. Fuentes, A. W. Cheever, E. J. Pearce, and T. A. Wynn Differential Regulation of Nitric Oxide Synthase-2 and Arginase-1 by Type 1/Type 2 Cytokines In Vivo: Granulomatous Pathology Is Shaped by the Pattern of L-Arginine Metabolism J. Immunol., December 1, 2001; 167(11): 6533 - 6544. [Abstract] [Full Text] [PDF]

				A. Zernecke, K. S. C. Weber, L. P. Erwig, D. C. Kluth, B. Schroppel, A. J. Rees, and C. Weber Combinatorial Model of Chemokine Involvement in Glomerular Monocyte Recruitment: Role of CXC Chemokine Receptor 2 in Infiltration During Nephrotoxic Nephritis J. Immunol., May 1, 2001; 166(9): 5755 - 5762. [Abstract] [Full Text] [PDF]

				D. C. Kluth, C. V. Ainslie, W. P. Pearce, S. Finlay, D. Clarke, I. Anegon, and A. J. Rees Macrophages Transfected with Adenovirus to Express IL-4 Reduce Inflammation in Experimental Glomerulonephritis J. Immunol., April 1, 2001; 166(7): 4728 - 4736. [Abstract] [Full Text] [PDF]