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. 1996 Mar;148(3):961–967.

Fibronectin is the major fibroblast chemoattractant in rabbit anti-glomerular basement membrane disease.

M Gharaee-Kermani 1, R Wiggins 1, F Wolber 1, M Goyal 1, S H Phan 1
PMCID: PMC1861713  PMID: 8774150

Abstract

The mechanism for fibroblast recruitment in renal fibrosis due to anti-glomerular basement membrane (anti-GBM) disease is unknown. Since fibroblast recruitment can occur via chemotaxis, assessment of the possible production of fibroblast chemotactic activity by affected renal tissue and its identification could provide important clues. Anti-GBM disease was induced by injection of guinea pig anti-rabbit GBM immunoglobulin G into rabbits previously sensitized to guinea pig immunoglobulin G. On days 4, 7, and 14 after induction, renal tissue was harvested and glomeruli isolated. Overnight serum-free conditioned media from whole cortex and glomeruli were prepared and assayed for fibroblast chemotactic activity. The results show low level activity in both conditioned media from control animals. In contrast, conditioned media from anti-GBM-treated animals at all time points showed significantly elevated fibroblast chemotactic activity peaking on day 4 with subsequent reduction thereafter. The magnitude of increase in cortical conditioned media was significantly higher than that for glomerular conditioned media, suggesting that most of the activity was derived from extraglomerular sources. Gel filtration analysis revealed the activity to be heterogeneous, consisting of at least four major species with estimated molecular weights ranging from 10 to > 100 kd. Acidification of conditioned media failed to increase chemotactic activity significantly, whereas protease digestion abolished it. Treatment of conditioned media with antifibronectin inhibited > 85% of the chemotactic activity, whereas antibodies to platelet-derived growth factor and transforming growth factor-beta did not have a significant effect. These findings taken together suggest that fibronectin-derived peptides represent the predominant fibroblast chemoattractant produced by renal cortex in anti-GBM disease.

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Selected References

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  1. Border W. A., Okuda S., Languino L. R., Ruoslahti E. Transforming growth factor-beta regulates production of proteoglycans by mesangial cells. Kidney Int. 1990 Feb;37(2):689–695. doi: 10.1038/ki.1990.35. [DOI] [PubMed] [Google Scholar]
  2. Brieland J. K., Jones M. L., Flory C. M., Miller G. R., Warren J. S., Phan S. H., Fantone J. C. Expression of monocyte chemoattractant protein-1 (MCP-1) by rat alveolar macrophages during chronic lung injury. Am J Respir Cell Mol Biol. 1993 Sep;9(3):300–305. doi: 10.1165/ajrcmb/9.3.300. [DOI] [PubMed] [Google Scholar]
  3. Clark R. A., Wikner N. E., Doherty D. E., Norris D. A. Cryptic chemotactic activity of fibronectin for human monocytes resides in the 120-kDa fibroblastic cell-binding fragment. J Biol Chem. 1988 Aug 25;263(24):12115–12123. [PubMed] [Google Scholar]
  4. Coimbra T., Wiggins R., Noh J. W., Merritt S., Phan S. H. Transforming growth factor-beta production in anti-glomerular basement membrane disease in the rabbit. Am J Pathol. 1991 Jan;138(1):223–234. [PMC free article] [PubMed] [Google Scholar]
  5. Denholm E. M., Lewis J. C. Monocyte chemoattractants in pigeon aortic atherosclerosis. Am J Pathol. 1987 Mar;126(3):464–475. [PMC free article] [PubMed] [Google Scholar]
  6. Denholm E. M., Wolber F. M., Phan S. H. Secretion of monocyte chemotactic activity by alveolar macrophages. Am J Pathol. 1989 Sep;135(3):571–580. [PMC free article] [PubMed] [Google Scholar]
  7. Denholm E. M., Wolber F. M., Phan S. H. Secretion of monocyte chemotactic activity by alveolar macrophages. Am J Pathol. 1989 Sep;135(3):571–580. [PMC free article] [PubMed] [Google Scholar]
  8. Downer G., Phan S. H., Wiggins R. C. Analysis of renal fibrosis in a rabbit model of crescentic nephritis. J Clin Invest. 1988 Sep;82(3):998–1006. doi: 10.1172/JCI113710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fine A., Goldstein R. H. The effect of transforming growth factor-beta on cell proliferation and collagen formation by lung fibroblasts. J Biol Chem. 1987 Mar 15;262(8):3897–3902. [PubMed] [Google Scholar]
  10. Glass B. J., Van Dis M. L., Langlais R. P., Miles D. A. Xerostomia: diagnosis and treatment planning considerations. Oral Surg Oral Med Oral Pathol. 1984 Aug;58(2):248–252. doi: 10.1016/0030-4220(84)90146-4. [DOI] [PubMed] [Google Scholar]
  11. Glassroth J. L., Bernardo J., Lucey E. C., Center D. M., Jung-Legg Y. J., Snider G. L. Interstitial pulmonary fibrosis induced in hamsters by intratracheally administered chrysotile asbestos. Histology, lung mechanics, and inflammatory events. Am Rev Respir Dis. 1984 Aug;130(2):242–248. doi: 10.1164/arrd.1984.130.2.242. [DOI] [PubMed] [Google Scholar]
  12. Goyal M., Wiggins R. Fibronectin mRNA and protein accumulation, distribution, and breakdown in rabbit anti-glomerular basement membrane disease. J Am Soc Nephrol. 1991 Jun;1(12):1334–1342. doi: 10.1681/ASN.V1121334. [DOI] [PubMed] [Google Scholar]
  13. Ignotz R. A., Massagué J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337–4345. [PubMed] [Google Scholar]
  14. Kagan E., Oghiso Y., Hartmann D. P. Enhanced release of a chemoattractant for alveolar macrophages after asbestos inhalation. Am Rev Respir Dis. 1983 Oct;128(4):680–687. doi: 10.1164/arrd.1983.128.4.680. [DOI] [PubMed] [Google Scholar]
  15. Katsuoka K., Hein R., Krieg T., Schell H., Hornstein O. P. Trichilemmoid carcinoma-derived cells produce a growth factor for fibroblasts and reveal fibroblast chemotactic activity. Arch Dermatol Res. 1987;279(6):418–420. doi: 10.1007/BF00412631. [DOI] [PubMed] [Google Scholar]
  16. Koyama N., Watanabe S., Tezuka M., Morisaki N., Saito Y., Yoshida S. Migratory and proliferative effect of platelet-derived growth factor in rabbit retinal endothelial cells: evidence of an autocrine pathway of platelet-derived growth factor. J Cell Physiol. 1994 Jan;158(1):1–6. doi: 10.1002/jcp.1041580102. [DOI] [PubMed] [Google Scholar]
  17. Lawrence D. A., Pircher R., Jullien P. Conversion of a high molecular weight latent beta-TGF from chicken embryo fibroblasts into a low molecular weight active beta-TGF under acidic conditions. Biochem Biophys Res Commun. 1985 Dec 31;133(3):1026–1034. doi: 10.1016/0006-291x(85)91239-2. [DOI] [PubMed] [Google Scholar]
  18. Lawrence D. A., Pircher R., Jullien P. Conversion of a high molecular weight latent beta-TGF from chicken embryo fibroblasts into a low molecular weight active beta-TGF under acidic conditions. Biochem Biophys Res Commun. 1985 Dec 31;133(3):1026–1034. doi: 10.1016/0006-291x(85)91239-2. [DOI] [PubMed] [Google Scholar]
  19. Lugano E. M., Dauber J. H., Daniele R. P. Silica stimulation of chemotactic factor release by guinea pig alveolar macrophages. J Reticuloendothel Soc. 1981 Nov;30(5):381–390. [PubMed] [Google Scholar]
  20. Lukacs N. W., Chensue S. W., Smith R. E., Strieter R. M., Warmington K., Wilke C., Kunkel S. L. Production of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 alpha by inflammatory granuloma fibroblasts. Am J Pathol. 1994 Apr;144(4):711–718. [PMC free article] [PubMed] [Google Scholar]
  21. MacKay K., Striker L. J., Stauffer J. W., Doi T., Agodoa L. Y., Striker G. E. Transforming growth factor-beta. Murine glomerular receptors and responses of isolated glomerular cells. J Clin Invest. 1989 Apr;83(4):1160–1167. doi: 10.1172/JCI113996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Martinet Y., Rom W. N., Grotendorst G. R., Martin G. R., Crystal R. G. Exaggerated spontaneous release of platelet-derived growth factor by alveolar macrophages from patients with idiopathic pulmonary fibrosis. N Engl J Med. 1987 Jul 23;317(4):202–209. doi: 10.1056/NEJM198707233170404. [DOI] [PubMed] [Google Scholar]
  23. Mensing H., Pontz B. F., Müller P. K., Gauss-Müller V. A study on fibroblast chemotaxis using fibronectin and conditioned medium as chemoattractants. Eur J Cell Biol. 1983 Jan;29(2):268–273. [PubMed] [Google Scholar]
  24. Merritt S. E., Killen P. D., Phan S. H., Wiggins R. C. Analysis of alpha 1 (I) procollagen alpha 1 (IV) collagen, and beta-actin mRNA in glomerulus and cortex of rabbits with experimental anti-glomerular basement membrane disease. Evidence for early extraglomerular collagen biosynthesis. Lab Invest. 1990 Dec;63(6):762–769. [PubMed] [Google Scholar]
  25. Miller K., Calverley A., Kagan E. Evidence of a quartz-induced chemotactic factor for guinea pig alveolar macrophages. Environ Res. 1980 Jun;22(1):31–39. doi: 10.1016/0013-9351(80)90116-4. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Nickeleit V., Zagachin L., Nishikawa K., Peters J. H., Hynes R. O., Colvin R. B. Embryonic fibronectin isoforms are synthesized in crescents in experimental autoimmune glomerulonephritis. Am J Pathol. 1995 Oct;147(4):965–978. [PMC free article] [PubMed] [Google Scholar]
  28. Norris D. A., Clark R. A., Swigart L. M., Huff J. C., Weston W. L., Howell S. E. Fibronectin fragment(s) are chemotactic for human peripheral blood monocytes. J Immunol. 1982 Oct;129(4):1612–1618. [PubMed] [Google Scholar]
  29. Okada F., Yamaguchi K., Ichihara A., Nakamura T. One of two subunits of masking protein in latent TGF-beta is a part of pro-TGF-beta. FEBS Lett. 1989 Jan 2;242(2):240–244. doi: 10.1016/0014-5793(89)80477-6. [DOI] [PubMed] [Google Scholar]
  30. Okada F., Yamaguchi K., Ichihara A., Nakamura T. One of two subunits of masking protein in latent TGF-beta is a part of pro-TGF-beta. FEBS Lett. 1989 Jan 2;242(2):240–244. doi: 10.1016/0014-5793(89)80477-6. [DOI] [PubMed] [Google Scholar]
  31. Okuda S., Languino L. R., Ruoslahti E., Border W. A. Elevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix. J Clin Invest. 1990 Aug;86(2):453–462. doi: 10.1172/JCI114731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Phan S. H., Gharaee-Kermani M., McGarry B., Kunkel S. L., Wolber F. W. Regulation of rat pulmonary artery endothelial cell transforming growth factor-beta production by IL-1 beta and tumor necrosis factor-alpha. J Immunol. 1992 Jul 1;149(1):103–106. [PubMed] [Google Scholar]
  33. Phan S. H., Gharaee-Kermani M., Wolber F., Ryan U. S. Stimulation of rat endothelial cell transforming growth factor-beta production by bleomycin. J Clin Invest. 1991 Jan;87(1):148–154. doi: 10.1172/JCI114964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Phan S. H., McGarry B. M., Loeffler K. M., Kunkel S. L. Regulation of macrophage-derived fibroblast growth factor release by arachidonate metabolites. J Leukoc Biol. 1987 Aug;42(2):106–113. doi: 10.1002/jlb.42.2.106. [DOI] [PubMed] [Google Scholar]
  35. Phan S. H., Varani J., Smith D. Rat lung fibroblast collagen metabolism in bleomycin-induced pulmonary fibrosis. J Clin Invest. 1985 Jul;76(1):241–247. doi: 10.1172/JCI111953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rennard S. I., Hunninghake G. W., Bitterman P. B., Crystal R. G. Production of fibronectin by the human alveolar macrophage: mechanism for the recruitment of fibroblasts to sites of tissue injury in interstitial lung diseases. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7147–7151. doi: 10.1073/pnas.78.11.7147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schoenberger C. I., Rennard S. I., Bitterman P. B., Fukuda Y., Ferrans V. J., Crystal R. G. Paraquat-induced pulmonary fibrosis. Role of the alveolitis in modulating the development of fibrosis. Am Rev Respir Dis. 1984 Jan;129(1):168–173. doi: 10.1164/arrd.1984.129.1.168. [DOI] [PubMed] [Google Scholar]
  38. Senior R. M., Huang J. S., Griffin G. L., Deuel T. F. Dissociation of the chemotactic and mitogenic activities of platelet-derived growth factor by human neutrophil elastase. J Cell Biol. 1985 Feb;100(2):351–356. doi: 10.1083/jcb.100.2.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Shoji S., Rickard K. A., Ertl R. F., Robbins R. A., Linder J., Rennard S. I. Bronchial epithelial cells produce lung fibroblast chemotactic factor: fibronectin. Am J Respir Cell Mol Biol. 1989 Jul;1(1):13–20. doi: 10.1165/ajrcmb/1.1.13. [DOI] [PubMed] [Google Scholar]
  40. Uchiyama T., Ito A., Ikesue A., Nakagawa H., Mori Y. Chemotactic factor in the pregnant rabbit uterine cervix. Am J Obstet Gynecol. 1992 Nov;167(5):1417–1422. doi: 10.1016/s0002-9378(11)91727-x. [DOI] [PubMed] [Google Scholar]
  41. Van den Eijnden-Van Raaij A. J., Koornneef I., Van Oostwaard T. M., Feyen A., Kruijer W., De Laat S. W., Van Zoelen E. J. Purification of a growth factor related to platelet-derived growth factor and a type beta transforming growth factor secreted by mouse neuroblastoma cells. A general strategy for the purification of basic polypeptide growth factors. Biochem J. 1989 Jan 15;257(2):375–382. doi: 10.1042/bj2570375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Van den Eijnden-Van Raaij A. J., Koornneef I., Van Oostwaard T. M., Feyen A., Kruijer W., De Laat S. W., Van Zoelen E. J. Purification of a growth factor related to platelet-derived growth factor and a type beta transforming growth factor secreted by mouse neuroblastoma cells. A general strategy for the purification of basic polypeptide growth factors. Biochem J. 1989 Jan 15;257(2):375–382. doi: 10.1042/bj2570375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Vissers M. C., Winterbourn C. C., Hunt J. S. Degradation of glomerular basement membrane by human neutrophils in vitro. Biochim Biophys Acta. 1984 Jun 19;804(2):154–160. doi: 10.1016/0167-4889(84)90144-7. [DOI] [PubMed] [Google Scholar]
  44. Wang J. M., Colella S., Allavena P., Mantovani A. Chemotactic activity of human recombinant granulocyte-macrophage colony-stimulating factor. Immunology. 1987 Mar;60(3):439–444. [PMC free article] [PubMed] [Google Scholar]
  45. Wiggins R. C., Glatfelter A., Brukman J. Procoagulant activity in glomeruli and urine of rabbits with nephrotoxic nephritis. Lab Invest. 1985 Aug;53(2):156–165. [PubMed] [Google Scholar]
  46. Wiggins R., Glatfelter A., Kshirsagar B., Beals T. Lipid microvesicles and their association with procoagulant activity in urine and glomeruli of rabbits with nephrotoxic nephritis. Lab Invest. 1987 Mar;56(3):264–272. [PubMed] [Google Scholar]
  47. Wiggins R., Goyal M., Merritt S., Killen P. D. Vascular adventitial cell expression of collagen I messenger ribonucleic acid in anti-glomerular basement membrane antibody-induced crescentic nephritis in the rabbit. A cellular source for interstitial collagen synthesis in inflammatory renal disease. Lab Invest. 1993 May;68(5):557–565. [PubMed] [Google Scholar]
  48. Yamauchi K., Martinet Y., Crystal R. G. Modulation of fibronectin gene expression in human mononuclear phagocytes. J Clin Invest. 1987 Dec;80(6):1720–1727. doi: 10.1172/JCI113263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yoshimura T., Takeya M., Takahashi K. Molecular cloning of rat monocyte chemoattractant protein-1 (MCP-1) and its expression in rat spleen cells and tumor cell lines. Biochem Biophys Res Commun. 1991 Jan 31;174(2):504–509. doi: 10.1016/0006-291x(91)91445-i. [DOI] [PubMed] [Google Scholar]
  50. Yoshioka K., Takemura T., Murakami K., Okada M., Hino S., Miyamoto H., Maki S. Transforming growth factor-beta protein and mRNA in glomeruli in normal and diseased human kidneys. Lab Invest. 1993 Feb;68(2):154–163. [PubMed] [Google Scholar]
  51. Zhang K., Gharaee-Kermani M., Jones M. L., Warren J. S., Phan S. H. Lung monocyte chemoattractant protein-1 gene expression in bleomycin-induced pulmonary fibrosis. J Immunol. 1994 Nov 15;153(10):4733–4741. [PubMed] [Google Scholar]
  52. Zhang K., Gharaee-Kermani M., McGarry B., Phan S. H. In situ hybridization analysis of rat lung alpha 1(I) and alpha 2(I) collagen gene expression in pulmonary fibrosis induced by endotracheal bleomycin injection. Lab Invest. 1994 Feb;70(2):192–202. [PubMed] [Google Scholar]
  53. Zhang K., Rekhter M. D., Gordon D., Phan S. H. Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study. Am J Pathol. 1994 Jul;145(1):114–125. [PMC free article] [PubMed] [Google Scholar]

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