Abstract
The chemotactic factors responsible for complement-independent macrophage accumulation in immune-complex diseases such as glomerulonephritis remain unknown. Fc receptors for IgG complexes are found on mesangial cells of the kidney, which produce the macrophage growth factor colony-stimulating factor 1 (CSF-1). We therefore investigated the possible stimulation of mesangial-cell expression of CSF-1 and the recently identified monocyte-specific chemoattractant protein 1 (MCP-1) by IgG complexes. IgG complexes, but not monomeric IgG or F(ab')2 fragments of IgG, rapidly (2-8 h) increased mRNA for both CSF-1 (10-fold) and MCP-1 (20-fold) in cultured mouse mesangial cells. The increase of mRNA for CSF-1 and MCP-1 was not reduced by either cytochalasin B or D, indicating that Fc receptor occupancy is sufficient for signaling and that phagocytosis is not required to elicit this response. IgG complexes also caused a 10-fold increase in the secretion of CSF-1 and a 3- to 5-fold increase in secretion of MCP-1 into the cell culture medium. The synthesis and release of CSF-1 and MCP-1 by mesangial cells as a consequence of Fc receptor occupancy may be responsible for macrophage recruitment and activation at sites of immune-complex deposition.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Border W. A., Okuda S., Languino L. R., Sporn M. B., Ruoslahti E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1. Nature. 1990 Jul 26;346(6282):371–374. doi: 10.1038/346371a0. [DOI] [PubMed] [Google Scholar]
- Cooper J. A. Effects of cytochalasin and phalloidin on actin. J Cell Biol. 1987 Oct;105(4):1473–1478. doi: 10.1083/jcb.105.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guilbert L. J., Stanley E. R. The interaction of 125I-colony-stimulating factor-1 with bone marrow-derived macrophages. J Biol Chem. 1986 Mar 25;261(9):4024–4032. [PubMed] [Google Scholar]
- Holdsworth S. R., Neale T. J., Wilson C. B. Abrogation of macrophage-dependent injury in experimental glomerulonephritis in the rabbit. Use of an antimacrophage serum. J Clin Invest. 1981 Sep;68(3):686–698. doi: 10.1172/JCI110304. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunsicker L. G., Shearer T. P., Plattner S. B., Weisenburger D. The role of monocytes in serum sickness nephritis. J Exp Med. 1979 Sep 19;150(3):413–425. doi: 10.1084/jem.150.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ladner M. B., Martin G. A., Noble J. A., Wittman V. P., Warren M. K., McGrogan M., Stanley E. R. cDNA cloning and expression of murine macrophage colony-stimulating factor from L929 cells. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6706–6710. doi: 10.1073/pnas.85.18.6706. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leonard E. J., Yoshimura T. Human monocyte chemoattractant protein-1 (MCP-1). Immunol Today. 1990 Mar;11(3):97–101. doi: 10.1016/0167-5699(90)90035-8. [DOI] [PubMed] [Google Scholar]
- Lewis V. A., Koch T., Plutner H., Mellman I. A complementary DNA clone for a macrophage-lymphocyte Fc receptor. 1986 Nov 27-Dec 3Nature. 324(6095):372–375. doi: 10.1038/324372a0. [DOI] [PubMed] [Google Scholar]
- Mori T., Bartocci A., Satriano J., Zuckerman A., Stanley R., Santiago A., Schlondorff D. Mouse mesangial cells produce colony-stimulating factor-1 (CSF-1) and express the CSF-1 receptor. J Immunol. 1990 Jun 15;144(12):4697–4702. [PubMed] [Google Scholar]
- Neuwirth R., Singhal P., Diamond B., Hays R. M., Lobmeyer L., Clay K., Schlondorff D. Evidence for immunoglobulin Fc receptor-mediated prostaglandin2 and platelet-activating factor formation by cultured rat mesangial cells. J Clin Invest. 1988 Sep;82(3):936–944. doi: 10.1172/JCI113701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ravetch J. V., Kinet J. P. Fc receptors. Annu Rev Immunol. 1991;9:457–492. doi: 10.1146/annurev.iy.09.040191.002325. [DOI] [PubMed] [Google Scholar]
- Ravetch J. V., Luster A. D., Weinshank R., Kochan J., Pavlovec A., Portnoy D. A., Hulmes J., Pan Y. C., Unkeless J. C. Structural heterogeneity and functional domains of murine immunoglobulin G Fc receptors. Science. 1986 Nov 7;234(4777):718–725. doi: 10.1126/science.2946078. [DOI] [PubMed] [Google Scholar]
- Rollins B. J., Morrison E. D., Stiles C. D. Cloning and expression of JE, a gene inducible by platelet-derived growth factor and whose product has cytokine-like properties. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3738–3742. doi: 10.1073/pnas.85.11.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rollins B. J., Morton C. C., Ledbetter D. H., Eddy R. L., Jr, Shows T. B. Assignment of the human small inducible cytokine A2 gene, SCYA2 (encoding JE or MCP-1), to 17q11.2-12: evolutionary relatedness of cytokines clustered at the same locus. Genomics. 1991 Jun;10(2):489–492. doi: 10.1016/0888-7543(91)90338-f. [DOI] [PubMed] [Google Scholar]
- Rollins B. J., Stier P., Ernst T., Wong G. G. The human homolog of the JE gene encodes a monocyte secretory protein. Mol Cell Biol. 1989 Nov;9(11):4687–4695. doi: 10.1128/mcb.9.11.4687. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rollins B. J., Yoshimura T., Leonard E. J., Pober J. S. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am J Pathol. 1990 Jun;136(6):1229–1233. [PMC free article] [PubMed] [Google Scholar]
- Rousseaux J., Rousseaux-Prevost R., Bazin H. Optimal conditions for the preparation of proteolytic fragments from monoclonal IgG of different rat IgG subclasses. Methods Enzymol. 1986;121:663–669. doi: 10.1016/0076-6879(86)21065-4. [DOI] [PubMed] [Google Scholar]
- Santiago A., Mori T., Satriano J., Schlondorff D. Regulation of Fc receptors for IgG on cultured rat mesangial cells. Kidney Int. 1991 Jan;39(1):87–94. doi: 10.1038/ki.1991.11. [DOI] [PubMed] [Google Scholar]
- Santiago A., Satriano J., DeCandido S., Holthofer H., Schreiber R., Unkeless J., Schlondorff D. A specific Fc gamma receptor on cultured rat mesangial cells. J Immunol. 1989 Oct 15;143(8):2575–2582. [PubMed] [Google Scholar]
- Schlondorff D., Mori T. Contributions of mesangial cells to glomerular immune functions. Klin Wochenschr. 1990 Nov 16;68(22):1138–1144. doi: 10.1007/BF01798065. [DOI] [PubMed] [Google Scholar]
- Schlondorff D. The glomerular mesangial cell: an expanding role for a specialized pericyte. FASEB J. 1987 Oct;1(4):272–281. doi: 10.1096/fasebj.1.4.3308611. [DOI] [PubMed] [Google Scholar]
- Schreiner G. F., Unanue E. R. Origin of the rat mesangial phagocyte and its expression of the leukocyte common antigen. Lab Invest. 1984 Nov;51(5):515–523. [PubMed] [Google Scholar]
- Sedor J. R., Carey S. W., Emancipator S. N. Immune complexes bind to cultured rat glomerular mesangial cells to stimulate superoxide release. Evidence for an Fc receptor. J Immunol. 1987 Jun 1;138(11):3751–3757. [PubMed] [Google Scholar]
- Singhal P. C., Ding G. H., DeCandido S., Franki N., Hays R. M., Schlondorff D. Endocytosis by cultured mesangial cells and associated changes in prostaglandin E2 synthesis. Am J Physiol. 1987 Apr;252(4 Pt 2):F627–F634. doi: 10.1152/ajprenal.1987.252.4.F627. [DOI] [PubMed] [Google Scholar]
- Singhal P. C., Santiago A., Satriano J., Hays R. M., Schlondorff D. Effects of vasoactive agents on uptake of immunoglobulin G complexes by mesangial cells. Am J Physiol. 1990 Mar;258(3 Pt 2):F589–F596. doi: 10.1152/ajprenal.1990.258.3.F589. [DOI] [PubMed] [Google Scholar]
- Stanley E. R., Guilbert L. J., Tushinski R. J., Bartelmez S. H. CSF-1--a mononuclear phagocyte lineage-specific hemopoietic growth factor. J Cell Biochem. 1983;21(2):151–159. doi: 10.1002/jcb.240210206. [DOI] [PubMed] [Google Scholar]
- Tushinski R. J., Oliver I. T., Guilbert L. J., Tynan P. W., Warner J. R., Stanley E. R. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell. 1982 Jan;28(1):71–81. doi: 10.1016/0092-8674(82)90376-2. [DOI] [PubMed] [Google Scholar]
- Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Unkeless J. C., Scigliano E., Freedman V. H. Structure and function of human and murine receptors for IgG. Annu Rev Immunol. 1988;6:251–281. doi: 10.1146/annurev.iy.06.040188.001343. [DOI] [PubMed] [Google Scholar]
- Wiggins R. C., Cochrane C. G. Immune-complex-mediated biologic effects. N Engl J Med. 1981 Feb 26;304(9):518–520. doi: 10.1056/NEJM198102263040904. [DOI] [PubMed] [Google Scholar]
- Yoshimura T., Robinson E. A., Tanaka S., Appella E., Leonard E. J. Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. J Immunol. 1989 Mar 15;142(6):1956–1962. [PubMed] [Google Scholar]
- Yoshimura T., Yuhki N., Moore S. K., Appella E., Lerman M. I., Leonard E. J. Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett. 1989 Feb 27;244(2):487–493. doi: 10.1016/0014-5793(89)80590-3. [DOI] [PubMed] [Google Scholar]
- 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]