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. 1995 Mar;95(3):1009–1017. doi: 10.1172/JCI117745

Modulation of neutrophil influx in glomerulonephritis in the rat with anti-macrophage inflammatory protein-2 (MIP-2) antibody.

L Feng 1, Y Xia 1, T Yoshimura 1, C B Wilson 1
PMCID: PMC441434  PMID: 7883948

Abstract

The role of the chemokine, macrophage inflammatory protein-2 (MIP-2), during anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was studied. Rat MIP-2 cDNA had been cloned previously. Recombinant rat MIP-2 (rMIP-2) from Escherichia coli exhibited neutrophil chemotactic activity and produced neutrophil influx when injected into the rat bladder wall. By using a riboprobe derived from the cDNA and an anti-rMIP-2 polyclonal Ab, MIP-2 was found to be induced in glomeruli with anti-GBM Ab GN as mRNA by 30 min and protein by 4 h, with both disappearing by 24 h. The expression of MIP-2 correlated with glomerular neutrophil influx. A single dose of the anti-MIP-2 Ab 30 min before anti-GBM Ab was effective in reducing neutrophil influx (40% at 4 h, P < 0.01) and periodic acid-Schiff deposits containing fibrin (54% at 24 h, P < 0.01). The anti-rMIP-2 Ab had no effect on anti-GBM Ab binding (paired-label isotope study). Functional improvement in the glomerular damage was evidenced by a reduction of abnormal proteinuria (P < 0.05). These results suggest that MIP-2 is a major neutrophil chemoattractant contributing to influx of neutrophils in Ab-induced glomerular inflammation in the rat.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbott F., Ryan J. J., Ceska M., Matsushima K., Sarraf C. E., Rees A. J. Interleukin-1 beta stimulates human mesangial cells to synthesize and release interleukins-6 and -8. Kidney Int. 1991 Oct;40(4):597–605. doi: 10.1038/ki.1991.250. [DOI] [PubMed] [Google Scholar]
  2. Albelda S. M. Endothelial and epithelial cell adhesion molecules. Am J Respir Cell Mol Biol. 1991 Mar;4(3):195–203. doi: 10.1165/ajrcmb/4.3.195. [DOI] [PubMed] [Google Scholar]
  3. Appelberg R. Macrophage inflammatory proteins MIP-1 and MIP-2 are involved in T cell-mediated neutrophil recruitment. J Leukoc Biol. 1992 Sep;52(3):303–306. doi: 10.1002/jlb.52.3.303. [DOI] [PubMed] [Google Scholar]
  4. Bevilacqua M. P. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol. 1993;11:767–804. doi: 10.1146/annurev.iy.11.040193.004003. [DOI] [PubMed] [Google Scholar]
  5. Blantz R. C., Wilson C. B. Acute effects of antiglomerular basement membrane antibody on the process of glomerular filtration in the rat. J Clin Invest. 1976 Oct;58(4):899–911. doi: 10.1172/JCI108543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brady H. R., Denton M. D., Jimenez W., Takata S., Palliser D., Brenner B. M. Chemoattractants provoke monocyte adhesion to human mesangial cells and mesangial cell injury. Kidney Int. 1992 Aug;42(2):480–487. doi: 10.1038/ki.1992.312. [DOI] [PubMed] [Google Scholar]
  7. Brady H. R., Spertini O., Jimenez W., Brenner B. M., Marsden P. A., Tedder T. F. Neutrophils, monocytes, and lymphocytes bind to cytokine-activated kidney glomerular endothelial cells through L-selectin (LAM-1) in vitro. J Immunol. 1992 Oct 1;149(7):2437–2444. [PubMed] [Google Scholar]
  8. Briscoe D. M., Cotran R. S. Role of leukocyte-endothelial cell adhesion molecules in renal inflammation: in vitro and in vivo studies. Kidney Int Suppl. 1993 Jul;42:S27–S34. [PubMed] [Google Scholar]
  9. Brown Z., Strieter R. M., Chensue S. W., Ceska M., Lindley I., Neild G. H., Kunkel S. L., Westwick J. Cytokine-activated human mesangial cells generate the neutrophil chemoattractant, interleukin 8. Kidney Int. 1991 Jul;40(1):86–90. doi: 10.1038/ki.1991.184. [DOI] [PubMed] [Google Scholar]
  10. Brown Z., Strieter R. M., Neild G. H., Thompson R. C., Kunkel S. L., Westwick J. IL-1 receptor antagonist inhibits monocyte chemotactic peptide 1 generation by human mesangial cells. Kidney Int. 1992 Jul;42(1):95–101. doi: 10.1038/ki.1992.266. [DOI] [PubMed] [Google Scholar]
  11. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  12. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  13. Chow J., Hartley R. B., Jagger C., Dilly S. A. ICAM-1 expression in renal disease. J Clin Pathol. 1992 Oct;45(10):880–884. doi: 10.1136/jcp.45.10.880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cotran R. S., Pober J. S. Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. J Am Soc Nephrol. 1990 Sep;1(3):225–235. doi: 10.1681/ASN.V13225. [DOI] [PubMed] [Google Scholar]
  15. Denton M. D., Marsden P. A., Luscinskas F. W., Brenner B. M., Brady H. R. Cytokine-induced phagocyte adhesion to human mesangial cells: role of CD11/CD18 integrins and ICAM-1. Am J Physiol. 1991 Dec;261(6 Pt 2):F1071–F1079. doi: 10.1152/ajprenal.1991.261.6.F1071. [DOI] [PubMed] [Google Scholar]
  16. Devery J. M., King N. J., Geczy C. L. Acute inflammatory activity of the S100 protein CP-10. Activation of neutrophils in vivo and in vitro. J Immunol. 1994 Feb 15;152(4):1888–1897. [PubMed] [Google Scholar]
  17. Feng L., Sun W., Xia Y., Tang W. W., Chanmugam P., Soyoola E., Wilson C. B., Hwang D. Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression. Arch Biochem Biophys. 1993 Dec;307(2):361–368. doi: 10.1006/abbi.1993.1601. [DOI] [PubMed] [Google Scholar]
  18. Feng L., Tang W. W., Loskutoff D. J., Wilson C. B. Dysfunction of glomerular fibrinolysis in experimental antiglomerular basement membrane antibody glomerulonephritis. J Am Soc Nephrol. 1993 May;3(11):1753–1764. doi: 10.1681/ASN.V3111753. [DOI] [PubMed] [Google Scholar]
  19. Feng L., Xia Y., Kreisberg J. I., Wilson C. B. Interleukin-1 alpha stimulates KC synthesis in rat mesangial cells: glucocorticoids inhibit KC induction by IL-1. Am J Physiol. 1994 May;266(5 Pt 2):F713–F722. doi: 10.1152/ajprenal.1994.266.5.F713. [DOI] [PubMed] [Google Scholar]
  20. Feng L., Xia Y., Wilson C. B. Alternative splicing of the NC1 domain of the human alpha 3(IV) collagen gene. Differential expression of mRNA transcripts that predict three protein variants with distinct carboxyl regions. J Biol Chem. 1994 Jan 21;269(3):2342–2348. [PubMed] [Google Scholar]
  21. Garner C. M., Richards G. M., Adu D., Pall A. A., Taylor C. M., Richards N. T., Michael J. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and function on cultured human glomerular epithelial cells. Clin Exp Immunol. 1994 Feb;95(2):322–326. doi: 10.1111/j.1365-2249.1994.tb06531.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Goto K., Nakamura S., Goto F., Yoshinaga M. Generation of an interleukin-I-like lymphocyte-stimulating factor at inflammatory sites: correlation with the infiltration of polymorphonuclear leucocytes. Br J Exp Pathol. 1984 Oct;65(5):521–532. [PMC free article] [PubMed] [Google Scholar]
  23. Grandaliano G., Valente A. J., Rozek M. M., Abboud H. E. Gamma interferon stimulates monocyte chemotactic protein (MCP-1) in human mesangial cells. J Lab Clin Med. 1994 Feb;123(2):282–289. [PubMed] [Google Scholar]
  24. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  25. Gómez-Chiarri M., Hamilton T. A., Egido J., Emancipator S. N. Expression of IP-10, a lipopolysaccharide- and interferon-gamma-inducible protein, in murine mesangial cells in culture. Am J Pathol. 1993 Feb;142(2):433–439. [PMC free article] [PubMed] [Google Scholar]
  26. Haskill S., Peace A., Morris J., Sporn S. A., Anisowicz A., Lee S. W., Smith T., Martin G., Ralph P., Sager R. Identification of three related human GRO genes encoding cytokine functions. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7732–7736. doi: 10.1073/pnas.87.19.7732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hechtman D. H., Cybulsky M. I., Fuchs H. J., Baker J. B., Gimbrone M. A., Jr Intravascular IL-8. Inhibitor of polymorphonuclear leukocyte accumulation at sites of acute inflammation. J Immunol. 1991 Aug 1;147(3):883–892. [PubMed] [Google Scholar]
  28. Heeger P., Wolf G., Meyers C., Sun M. J., O'Farrell S. C., Krensky A. M., Neilson E. G. Isolation and characterization of cDNA from renal tubular epithelium encoding murine Rantes. Kidney Int. 1992 Jan;41(1):220–225. doi: 10.1038/ki.1992.31. [DOI] [PubMed] [Google Scholar]
  29. Hora K., Satriano J. A., Santiago A., Mori T., Stanley E. R., Shan Z., Schlondorff D. Receptors for IgG complexes activate synthesis of monocyte chemoattractant peptide 1 and colony-stimulating factor 1. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1745–1749. doi: 10.1073/pnas.89.5.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Huang S., Paulauskis J. D., Godleski J. J., Kobzik L. Expression of macrophage inflammatory protein-2 and KC mRNA in pulmonary inflammation. Am J Pathol. 1992 Oct;141(4):981–988. [PMC free article] [PubMed] [Google Scholar]
  31. Huber A. R., Kunkel S. L., Todd R. F., 3rd, Weiss S. J. Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science. 1991 Oct 4;254(5028):99–102. doi: 10.1126/science.1718038. [DOI] [PubMed] [Google Scholar]
  32. Iida N., Grotendorst G. R. Cloning and sequencing of a new gro transcript from activated human monocytes: expression in leukocytes and wound tissue. Mol Cell Biol. 1990 Oct;10(10):5596–5599. doi: 10.1128/mcb.10.10.5596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kawasaki K., Yaoita E., Yamamoto T., Tamatani T., Miyasaka M., Kihara I. Antibodies against intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 prevent glomerular injury in rat experimental crescentic glomerulonephritis. J Immunol. 1993 Feb 1;150(3):1074–1083. [PubMed] [Google Scholar]
  34. Kobzik L., Huang S., Paulauskis J. D., Godleski J. J. Particle opsonization and lung macrophage cytokine response. In vitro and in vivo analysis. J Immunol. 1993 Sep 1;151(5):2753–2759. [PubMed] [Google Scholar]
  35. Konishi K., Takata Y., Yamamoto M., Yomogida K., Watanabe K., Tsurufuji S., Fujioka M. Structure of the gene encoding rat neutrophil chemo-attractant Gro. Gene. 1993 Apr 30;126(2):285–286. doi: 10.1016/0378-1119(93)90382-d. [DOI] [PubMed] [Google Scholar]
  36. Kusner D. J., Luebbers E. L., Nowinski R. J., Konieczkowski M., King C. H., Sedor J. R. Cytokine- and LPS-induced synthesis of interleukin-8 from human mesangial cells. Kidney Int. 1991 Jun;39(6):1240–1248. doi: 10.1038/ki.1991.157. [DOI] [PubMed] [Google Scholar]
  37. Lackmann M., Cornish C. J., Simpson R. J., Moritz R. L., Geczy C. L. Purification and structural analysis of a murine chemotactic cytokine (CP-10) with sequence homology to S100 proteins. J Biol Chem. 1992 Apr 15;267(11):7499–7504. [PubMed] [Google Scholar]
  38. Lasky L. A. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992 Nov 6;258(5084):964–969. doi: 10.1126/science.1439808. [DOI] [PubMed] [Google Scholar]
  39. Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
  40. Miller M. D., Krangel M. S. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol. 1992;12(1-2):17–46. [PubMed] [Google Scholar]
  41. Mulligan M. S., Johnson K. J., Todd R. F., 3rd, Issekutz T. B., Miyasaka M., Tamatani T., Smith C. W., Anderson D. C., Ward P. A. Requirements for leukocyte adhesion molecules in nephrotoxic nephritis. J Clin Invest. 1993 Feb;91(2):577–587. doi: 10.1172/JCI116237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Müller G. A., Markovic-Lipkovski J., Müller C. A. Intercellular adhesion molecule-1 expression in human kidneys with glomerulonephritis. Clin Nephrol. 1991 Oct;36(4):203–208. [PubMed] [Google Scholar]
  43. Nishikawa K., Guo Y. J., Miyasaka M., Tamatani T., Collins A. B., Sy M. S., McCluskey R. T., Andres G. Antibodies to intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 prevent crescent formation in rat autoimmune glomerulonephritis. J Exp Med. 1993 Mar 1;177(3):667–677. doi: 10.1084/jem.177.3.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Osborn L. Leukocyte adhesion to endothelium in inflammation. Cell. 1990 Jul 13;62(1):3–6. doi: 10.1016/0092-8674(90)90230-c. [DOI] [PubMed] [Google Scholar]
  45. Pober J. S., Cotran R. S. Cytokines and endothelial cell biology. Physiol Rev. 1990 Apr;70(2):427–451. doi: 10.1152/physrev.1990.70.2.427. [DOI] [PubMed] [Google Scholar]
  46. Rosen S. D. Cell surface lectins in the immune system. Semin Immunol. 1993 Aug;5(4):237–247. doi: 10.1006/smim.1993.1028. [DOI] [PubMed] [Google Scholar]
  47. Rot A. Endothelial cell binding of NAP-1/IL-8: role in neutrophil emigration. Immunol Today. 1992 Aug;13(8):291–294. doi: 10.1016/0167-5699(92)90039-A. [DOI] [PubMed] [Google Scholar]
  48. Rovin B. H., Yoshiumura T., Tan L. Cytokine-induced production of monocyte chemoattractant protein-1 by cultured human mesangial cells. J Immunol. 1992 Apr 1;148(7):2148–2153. [PubMed] [Google Scholar]
  49. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Satriano J. A., Hora K., Shan Z., Stanley E. R., Mori T., Schlondorff D. Regulation of monocyte chemoattractant protein-1 and macrophage colony-stimulating factor-1 by IFN-gamma, tumor necrosis factor-alpha, IgG aggregates, and cAMP in mouse mesangial cells. J Immunol. 1993 Mar 1;150(5):1971–1978. [PubMed] [Google Scholar]
  51. Saukkonen K., Sande S., Cioffe C., Wolpe S., Sherry B., Cerami A., Tuomanen E. The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis. J Exp Med. 1990 Feb 1;171(2):439–448. doi: 10.1084/jem.171.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Schmouder R. L., Strieter R. M., Wiggins R. C., Chensue S. W., Kunkel S. L. In vitro and in vivo interleukin-8 production in human renal cortical epithelia. Kidney Int. 1992 Jan;41(1):191–198. doi: 10.1038/ki.1992.26. [DOI] [PubMed] [Google Scholar]
  53. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  54. Short J. M., Fernandez J. M., Sorge J. A., Huse W. D. Lambda ZAP: a bacteriophage lambda expression vector with in vivo excision properties. Nucleic Acids Res. 1988 Aug 11;16(15):7583–7600. doi: 10.1093/nar/16.15.7583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994 Jan 28;76(2):301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [PubMed] [Google Scholar]
  56. Stahl R. A., Thaiss F., Disser M., Helmchen U., Hora K., Schlöndorff D. Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephritis. Kidney Int. 1993 Nov;44(5):1036–1047. doi: 10.1038/ki.1993.346. [DOI] [PubMed] [Google Scholar]
  57. Tang W. W., Feng L., Vannice J. L., Wilson C. B. Interleukin-1 receptor antagonist ameliorates experimental anti-glomerular basement membrane antibody-associated glomerulonephritis. J Clin Invest. 1994 Jan;93(1):273–279. doi: 10.1172/JCI116956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Tekamp-Olson P., Gallegos C., Bauer D., McClain J., Sherry B., Fabre M., van Deventer S., Cerami A. Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. J Exp Med. 1990 Sep 1;172(3):911–919. doi: 10.1084/jem.172.3.911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Watanabe K., Konishi K., Fujioka M., Kinoshita S., Nakagawa H. The neutrophil chemoattractant produced by the rat kidney epithelioid cell line NRK-52E is a protein related to the KC/gro protein. J Biol Chem. 1989 Nov 25;264(33):19559–19563. [PubMed] [Google Scholar]
  60. Wen D. Z., Rowland A., Derynck R. Expression and secretion of gro/MGSA by stimulated human endothelial cells. EMBO J. 1989 Jun;8(6):1761–1766. doi: 10.1002/j.1460-2075.1989.tb03569.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Wilcox J. N. Fundamental principles of in situ hybridization. J Histochem Cytochem. 1993 Dec;41(12):1725–1733. doi: 10.1177/41.12.8245419. [DOI] [PubMed] [Google Scholar]
  62. Wilson C. B., Dixon F. J., Fortner J. G., Cerilli G. J. Glomerular basement membrane--reactive antibody in anti-lymphocyte globulin. J Clin Invest. 1971 Jul;50(7):1525–1535. doi: 10.1172/JCI106638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wolf G., Aberle S., Thaiss F., Nelson P. J., Krensky A. M., Neilson E. G., Stahl R. A. TNF alpha induces expression of the chemoattractant cytokine RANTES in cultured mouse mesangial cells. Kidney Int. 1993 Oct;44(4):795–804. doi: 10.1038/ki.1993.314. [DOI] [PubMed] [Google Scholar]
  64. Wu X., Wittwer A. J., Carr L. S., Crippes B. A., DeLarco J. E., Lefkowith J. B. Cytokine-induced neutrophil chemoattractant mediates neutrophil influx in immune complex glomerulonephritis in rat. J Clin Invest. 1994 Jul;94(1):337–344. doi: 10.1172/JCI117326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Wuthrich R. P., Jevnikar A. M., Takei F., Glimcher L. H., Kelley V. E. Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in autoimmune murine lupus nephritis. Am J Pathol. 1990 Feb;136(2):441–450. [PMC free article] [PubMed] [Google Scholar]
  66. Yoshimura T., Johnson D. G. cDNA cloning and expression of guinea pig neutrophil attractant protein-1 (NAP-1). NAP-1 is highly conserved in guinea pig. J Immunol. 1993 Dec 1;151(11):6225–6236. [PubMed] [Google Scholar]
  67. Yoshimura T., Yuhki N. Neutrophil attractant/activation protein-1 and monocyte chemoattractant protein-1 in rabbit. cDNA cloning and their expression in spleen cells. J Immunol. 1991 May 15;146(10):3483–3488. [PubMed] [Google Scholar]
  68. Yoshioka K., Takemura T., Murakami K., Okada M., Yagi K., Miyazato H., Matsushima K., Maki S. In situ expression of cytokines in IgA nephritis. Kidney Int. 1993 Oct;44(4):825–833. doi: 10.1038/ki.1993.317. [DOI] [PubMed] [Google Scholar]
  69. Zimmerman G. A., Prescott S. M., McIntyre T. M. Endothelial cell interactions with granulocytes: tethering and signaling molecules. Immunol Today. 1992 Mar;13(3):93–100. doi: 10.1016/0167-5699(92)90149-2. [DOI] [PubMed] [Google Scholar]
  70. Zoja C., Wang J. M., Bettoni S., Sironi M., Renzi D., Chiaffarino F., Abboud H. E., Van Damme J., Mantovani A., Remuzzi G. Interleukin-1 beta and tumor necrosis factor-alpha induce gene expression and production of leukocyte chemotactic factors, colony-stimulating factors, and interleukin-6 in human mesangial cells. Am J Pathol. 1991 Apr;138(4):991–1003. [PMC free article] [PubMed] [Google Scholar]

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