Monocyte Chemoattractant Protein-1 Promotes Macrophage-mediated Tubular Injury, but Not Glomerular Injury, in Nephrotoxic Serum Nephritis

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1999 Jan 12

PMID 9884336

Citations 64

Authors

G H Tesch

A Schwarting

K Kinoshita

H Y Lan

B J Rollins

V R Kelley

Affiliations

Soon will be listed here.

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is upregulated in renal parenchymal cells during kidney disease. To investigate whether MCP-1 promotes tubular and/or glomerular injury, we induced nephrotoxic serum nephritis (NSN) in MCP-1 genetically deficient mice. Mice were analyzed when tubules and glomeruli were severely damaged in the MCP-1-intact strain (day 7). MCP-1 transcripts increased fivefold in MCP-1-intact mice. MCP-1 was predominantly localized within cortical tubules (90%), and most cortical tubules were damaged, whereas few glomerular cells expressed MCP-1 (10%). By comparison, there was a marked reduction (>40%) in tubular injury in MCP-1-deficient mice (histopathology, apoptosis). MCP-1-deficient mice were not protected from glomerular injury (histopathology, proteinuria, macrophage influx). Macrophage accumulation increased adjacent to tubules in MCP-1-intact mice compared with MCP-1-deficient mice (70%, P < 0.005), indicating that macrophages recruited by MCP-1 induce tubular epithelial cell (TEC) damage. Lipopolysaccharide-activated bone marrow macrophages released molecules that induced TEC death that was not dependent on MCP-1 expression by macrophages or TEC. In conclusion, MCP-1 is predominantly expressed by TEC and not glomeruli, promotes TEC and not glomerular damage, and increases activated macrophages adjacent to TEC that damage TEC during NSN. Therefore, we suggest that blockage of TEC MCP-1 expression is a therapeutic strategy for some forms of kidney disease.

Citing Articles

Podocyte-Specific Deletion of MCP-1 Fails to Protect against Angiotensin II- or Adriamycin-Induced Glomerular Disease.

Bondi C, Hartman H, Rush B, Tan R Int J Mol Sci. 2024; 25(9).

PMID: 38732210 PMC: 11084322. DOI: 10.3390/ijms25094987.

Dietary Potassium Supplementation Reduces Chronic Kidney Lesions Independent of Blood Pressure in Deoxycorticosterone-Acetate and High Sodium Chloride-Treated Mice.

Wang Q, Schafer S, Haefliger J, Maillard M, Alonso F Int J Mol Sci. 2023; 24(23).

PMID: 38069178 PMC: 10705941. DOI: 10.3390/ijms242316858.

Macrophage Depletion Protects Against Cisplatin-Induced Ototoxicity and Nephrotoxicity.

Sung C, Hayase N, Yuen P, Lee J, Fernandez K, Hu X bioRxiv. 2023; .

PMID: 38014097 PMC: 10680818. DOI: 10.1101/2023.11.16.567274.

Soluble receptors for advanced glycation end-products prevent unilateral ureteral obstruction-induced renal fibrosis.

Kim C, Kang H, Kim G, Park J, Nam B, Park J Front Pharmacol. 2023; 14:1172269.

PMID: 37261287 PMC: 10227196. DOI: 10.3389/fphar.2023.1172269.

Meprin β expression modulates the interleukin-6 mediated JAK2-STAT3 signaling pathway in ischemia/reperfusion-induced kidney injury.

Abousaad S, Ahmed F, Abouzeid A, Ongeri E Physiol Rep. 2022; 10(18):e15468.

PMID: 36117389 PMC: 9483619. DOI: 10.14814/phy2.15468.

References

Sekiguchi M, Ou Z, Natori Y . Gene expression of CC chemokines in experimental crescentic glomerulonephritis (CGN). Clin Exp Immunol. 1997; 109(1):143-8. PMC: 1904711. DOI: 10.1046/j.1365-2249.1997.4271321.x. View

Tipping P, Huang X, Berndt M, Holdsworth S . A role for P selectin in complement-independent neutrophil-mediated glomerular injury. Kidney Int. 1994; 46(1):79-88. DOI: 10.1038/ki.1994.246. View

Stahl R, Thaiss F, Disser M, Helmchen U, Hora K, Schlondorff D . Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephritis. Kidney Int. 1993; 44(5):1036-47. DOI: 10.1038/ki.1993.346. View

Ma J, Xu J, Madaio M, Peng Q, Zhang J, Grewal I . Autoimmune lpr/lpr mice deficient in CD40 ligand: spontaneous Ig class switching with dichotomy of autoantibody responses. J Immunol. 1996; 157(1):417-26. View

Grandaliano G, Gesualdo L, Ranieri E, Monno R, Montinaro V, Marra F . Monocyte chemotactic peptide-1 expression in acute and chronic human nephritides: a pathogenetic role in interstitial monocytes recruitment. J Am Soc Nephrol. 1996; 7(6):906-13. DOI: 10.1681/ASN.V76906. View

Wada T, Yokoyama H, Su S, Mukaida N, Iwano M, Dohi K . Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis. Kidney Int. 1996; 49(3):761-7. DOI: 10.1038/ki.1996.105. View

Lu B, RUTLEDGE B, Gu L, Fiorillo J, Lukacs N, Kunkel S . Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J Exp Med. 1998; 187(4):601-8. PMC: 2212142. DOI: 10.1084/jem.187.4.601. View

Pichler R, Giachelli C, Lombardi D, Pippin J, Gordon K, Alpers C . Tubulointerstitial disease in glomerulonephritis. Potential role of osteopontin (uropontin). Am J Pathol. 1994; 144(5):915-26. PMC: 1887368. View

Rovin B, Phan L . Chemotactic factors and renal inflammation. Am J Kidney Dis. 1998; 31(6):1065-84. DOI: 10.1053/ajkd.1998.v31.pm9631856. View

10.

Franci C, Wong L, Van Damme J, Proost P, Charo I . Monocyte chemoattractant protein-3, but not monocyte chemoattractant protein-2, is a functional ligand of the human monocyte chemoattractant protein-1 receptor. J Immunol. 1995; 154(12):6511-7. View

11.

Grewal I, RUTLEDGE B, Fiorillo J, Gu L, Gladue R, Flavell R . Transgenic monocyte chemoattractant protein-1 (MCP-1) in pancreatic islets produces monocyte-rich insulitis without diabetes: abrogation by a second transgene expressing systemic MCP-1. J Immunol. 1997; 159(1):401-8. View

12.

Rovin B, Rumancik M, Tan L, Dickerson J . Glomerular expression of monocyte chemoattractant protein-1 in experimental and human glomerulonephritis. Lab Invest. 1994; 71(4):536-42. View

13.

Moore K, Naito T, Martin C, Kelley V . Enhanced response of macrophages to CSF-1 in autoimmune mice: a gene transfer strategy. J Immunol. 1996; 157(1):433-40. View

14.

Kurihara T, Warr G, Loy J, Bravo R . Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J Exp Med. 1997; 186(10):1757-62. PMC: 2199145. DOI: 10.1084/jem.186.10.1757. View

15.

Kuziel W, Morgan S, Dawson T, Griffin S, SMITHIES O, Ley K . Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc Natl Acad Sci U S A. 1997; 94(22):12053-8. PMC: 23699. DOI: 10.1073/pnas.94.22.12053. View

16.

Rovin B, Doe N, Tan L . Monocyte chemoattractant protein-1 levels in patients with glomerular disease. Am J Kidney Dis. 1996; 27(5):640-6. DOI: 10.1016/s0272-6386(96)90097-9. View

17.

Early G, Zhao W, Burns C . Anti-CD40 ligand antibody treatment prevents the development of lupus-like nephritis in a subset of New Zealand black x New Zealand white mice. Response correlates with the absence of an anti-antibody response. J Immunol. 1996; 157(7):3159-64. View

18.

Rovin B, Yoshiumura T, Tan L . Cytokine-induced production of monocyte chemoattractant protein-1 by cultured human mesangial cells. J Immunol. 1992; 148(7):2148-53. View

19.

Eddy A, Giachelli C . Renal expression of genes that promote interstitial inflammation and fibrosis in rats with protein-overload proteinuria. Kidney Int. 1995; 47(6):1546-57. DOI: 10.1038/ki.1995.218. View

20.

Tang W, Qi M, Warren J . Monocyte chemoattractant protein 1 mediates glomerular macrophage infiltration in anti-GBM Ab GN. Kidney Int. 1996; 50(2):665-71. DOI: 10.1038/ki.1996.363. View