Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1990 Nov 1;111(5):2139–2148. doi: 10.1083/jcb.111.5.2139

Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos, c-jun, and EGR2 mRNA

PMCID: PMC2116315  PMID: 2121746

Abstract

Adherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage. This differentiation is accompanied by an augmented capacity to generate growth factors. We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit (PDGF[B]) and transforming growth factor-beta (TGF- beta). After in vitro adherence, human monocytes had a biphasic increase in PDGF(B) mRNA with peaks at 6 h and 13 d. No increase in TGF- beta mRNA was observed. The 6-h increase in PDGF(B) mRNA was adherence dependent, and in addition, was abrogated when the cytoskeletal integrity was compromised by cytochalasin D. The 6-h increase in PDGF(B) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide. Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF(B) mRNA accumulation. The increased PDGF(B) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos (maximal at 20 min), c-jun, and EGR2 (maximal at 6-24 h). The increase in c-jun and EGR2, but not c-fos, mRNA was also abrogated by cytochalasin D. These observations suggest that adherence results in increases of c-fos, c-jun, EGR2, and PDGF(B) mRNA. In addition, the increases in c-jun, EGR2, and PDGF(B) may depend on cytoskeletal rearrangement. Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished.

Full Text

The Full Text of this article is available as a PDF (1.7 MB).

Selected References

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

  1. Assoian R. K., Fleurdelys B. E., Stevenson H. C., Miller P. J., Madtes D. K., Raines E. W., Ross R., Sporn M. B. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6020–6024. doi: 10.1073/pnas.84.17.6020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beckmann M. P., Betsholtz C., Heldin C. H., Westermark B., Di Marco E., Di Fiore P. P., Robbins K. C., Aaronson S. A. Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains. Science. 1988 Sep 9;241(4871):1346–1349. doi: 10.1126/science.2842868. [DOI] [PubMed] [Google Scholar]
  3. Ben-Ze'ev A. The role of changes in cell shape and contacts in the regulation of cytoskeleton expression during differentiation. J Cell Sci Suppl. 1987;8:293–312. doi: 10.1242/jcs.1987.supplement_8.16. [DOI] [PubMed] [Google Scholar]
  4. Bevilacqua M. P., Amrani D., Mosesson M. W., Bianco C. Receptors for cold-insoluble globulin (plasma fibronectin) on human monocytes. J Exp Med. 1981 Jan 1;153(1):42–60. doi: 10.1084/jem.153.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bissell M. J., Barcellos-Hoff M. H. The influence of extracellular matrix on gene expression: is structure the message? J Cell Sci Suppl. 1987;8:327–343. doi: 10.1242/jcs.1987.supplement_8.18. [DOI] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Clark R. A., Folkvord J. M., Hart C. E., Murray M. J., McPherson J. M. Platelet isoforms of platelet-derived growth factor stimulate fibroblasts to contract collagen matrices. J Clin Invest. 1989 Sep;84(3):1036–1040. doi: 10.1172/JCI114227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Collart M. A., Belin D., Vassalli J. D., Vassalli P. Modulations of functional activity in differentiated macrophages are accompanied by early and transient increase or decrease in c-fos gene transcription. J Immunol. 1987 Aug 1;139(3):949–955. [PubMed] [Google Scholar]
  9. Crystal R. G., Bitterman P. B., Rennard S. I., Hance A. J., Keogh B. A. Interstitial lung diseases of unknown cause. Disorders characterized by chronic inflammation of the lower respiratory tract (first of two parts). N Engl J Med. 1984 Jan 19;310(3):154–166. doi: 10.1056/NEJM198401193100304. [DOI] [PubMed] [Google Scholar]
  10. Doherty D. E., Haslett C., Tonnesen M. G., Henson P. M. Human monocyte adherence: a primary effect of chemotactic factors on the monocyte to stimulate adherence to human endothelium. J Immunol. 1987 Mar 15;138(6):1762–1771. [PubMed] [Google Scholar]
  11. Doherty D. E., Zagarella L., Henson P. M., Worthen G. S. Lipopolysaccharide stimulates monocyte adherence by effects on both the monocyte and the endothelial cell. J Immunol. 1989 Dec 1;143(11):3673–3679. [PubMed] [Google Scholar]
  12. Eierman D. F., Johnson C. E., Haskill J. S. Human monocyte inflammatory mediator gene expression is selectively regulated by adherence substrates. J Immunol. 1989 Mar 15;142(6):1970–1976. [PubMed] [Google Scholar]
  13. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Gay S., Jones R. E., Jr, Huang G. Q., Gay R. E. Immunohistologic demonstration of platelet-derived growth factor (PDGF) and sis-oncogene expression in scleroderma. J Invest Dermatol. 1989 Feb;92(2):301–303. doi: 10.1111/1523-1747.ep12276895. [DOI] [PubMed] [Google Scholar]
  16. Glisin V., Crkvenjakov R., Byus C. Ribonucleic acid isolated by cesium chloride centrifugation. Biochemistry. 1974 Jun 4;13(12):2633–2637. doi: 10.1021/bi00709a025. [DOI] [PubMed] [Google Scholar]
  17. Haskill S., Johnson C., Eierman D., Becker S., Warren K. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 1988 Mar 1;140(5):1690–1694. [PubMed] [Google Scholar]
  18. Haslett C., Guthrie L. A., Kopaniak M. M., Johnston R. B., Jr, Henson P. M. Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide. Am J Pathol. 1985 Apr;119(1):101–110. [PMC free article] [PubMed] [Google Scholar]
  19. Herman B., Pledger W. J. Platelet-derived growth factor-induced alterations in vinculin and actin distribution in BALB/c-3T3 cells. J Cell Biol. 1985 Apr;100(4):1031–1040. doi: 10.1083/jcb.100.4.1031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Horsburgh C. R., Jr, Clark R. A., Kirkpatrick C. H. Lymphokines and platelets promote human monocyte adherence to fibrinogen and fibronectin in vitro. J Leukoc Biol. 1987 Jan;41(1):14–24. doi: 10.1002/jlb.41.1.14. [DOI] [PubMed] [Google Scholar]
  21. Hosang M., Rouge M., Wipf B., Eggimann B., Kaufmann F., Hunziker W. Both homodimeric isoforms of PDGF (AA and BB) have mitogenic and chemotactic activity and stimulate phosphoinositol turnover. J Cell Physiol. 1989 Sep;140(3):558–564. doi: 10.1002/jcp.1041400322. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Joseph L. J., Le Beau M. M., Jamieson G. A., Jr, Acharya S., Shows T. B., Rowley J. D., Sukhatme V. P. Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with "zinc-binding finger" structure. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7164–7168. doi: 10.1073/pnas.85.19.7164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kaplan G., Gaudernack G. In vitro differentiation of human monocytes. Differences in monocyte phenotypes induced by cultivation on glass or on collagen. J Exp Med. 1982 Oct 1;156(4):1101–1114. doi: 10.1084/jem.156.4.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lawrence W. T., Norton J. A., Sporn M. B., Gorschboth C., Grotendorst G. R. The reversal of an Adriamycin induced healing impairment with chemoattractants and growth factors. Ann Surg. 1986 Feb;203(2):142–147. doi: 10.1097/00000658-198602000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lehto V. P., Hovi T., Vartio T., Badley R. A., Virtanen I. Reorganization of cytoskeletal and contractile elements during transition of human monocytes into adherent macrophages. Lab Invest. 1982 Oct;47(4):391–399. [PubMed] [Google Scholar]
  27. Lyons R. M., Keski-Oja J., Moses H. L. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J Cell Biol. 1988 May;106(5):1659–1665. doi: 10.1083/jcb.106.5.1659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Mitchell R. L., Zokas L., Schreiber R. D., Verma I. M. Rapid induction of the expression of proto-oncogene fos during human monocytic differentiation. Cell. 1985 Jan;40(1):209–217. doi: 10.1016/0092-8674(85)90324-1. [DOI] [PubMed] [Google Scholar]
  30. Miyazono K., Heldin C. H. Role for carbohydrate structures in TGF-beta 1 latency. Nature. 1989 Mar 9;338(6211):158–160. doi: 10.1038/338158a0. [DOI] [PubMed] [Google Scholar]
  31. Mornex J. F., Martinet Y., Yamauchi K., Bitterman P. B., Grotendorst G. R., Chytil-Weir A., Martin G. R., Crystal R. G. Spontaneous expression of the c-sis gene and release of a platelet-derived growth factorlike molecule by human alveolar macrophages. J Clin Invest. 1986 Jul;78(1):61–66. doi: 10.1172/JCI112574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Musson R. A. Human serum induces maturation of human monocytes in vitro. Changes in cytolytic activity, intracellular lysosomal enzymes, and nonspecific esterase activity. Am J Pathol. 1983 Jun;111(3):331–340. [PMC free article] [PubMed] [Google Scholar]
  33. Mustoe T. A., Pierce G. F., Thomason A., Gramates P., Sporn M. B., Deuel T. F. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science. 1987 Sep 11;237(4820):1333–1336. doi: 10.1126/science.2442813. [DOI] [PubMed] [Google Scholar]
  34. Müller R., Curran T., Müller D., Guilbert L. Induction of c-fos during myelomonocytic differentiation and macrophage proliferation. Nature. 1985 Apr 11;314(6011):546–548. doi: 10.1038/314546a0. [DOI] [PubMed] [Google Scholar]
  35. Müller R., Müller D., Guilbert L. Differential expression of c-fos in hematopoietic cells: correlation with differentiation of monomyelocytic cells in vitro. EMBO J. 1984 Aug;3(8):1887–1890. doi: 10.1002/j.1460-2075.1984.tb02063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nistér M., Hammacher A., Mellström K., Siegbahn A., Rönnstrand L., Westermark B., Heldin C. H. A glioma-derived PDGF A chain homodimer has different functional activities from a PDGF AB heterodimer purified from human platelets. Cell. 1988 Mar 25;52(6):791–799. doi: 10.1016/0092-8674(88)90421-7. [DOI] [PubMed] [Google Scholar]
  37. Olsen D. R., Uitto J. Differential expression of type IV procollagen and laminin genes by fetal vs adult skin fibroblasts in culture: determination of subunit mRNA steady-state levels. J Invest Dermatol. 1989 Jul;93(1):127–131. doi: 10.1111/1523-1747.ep12277381. [DOI] [PubMed] [Google Scholar]
  38. Pantazis P., Sariban E., Kufe D., Antoniades H. N. Induction of c-sis gene expression and synthesis of platelet-derived growth factor in human myeloid leukemia cells during monocytic differentiation. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6455–6459. doi: 10.1073/pnas.83.17.6455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Pierce G. F., Mustoe T. A., Senior R. M., Reed J., Griffin G. L., Thomason A., Deuel T. F. In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins. J Exp Med. 1988 Mar 1;167(3):974–987. doi: 10.1084/jem.167.3.974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Raghu G., Masta S., Meyers D., Narayanan A. S. Collagen synthesis by normal and fibrotic human lung fibroblasts and the effect of transforming growth factor-beta. Am Rev Respir Dis. 1989 Jul;140(1):95–100. doi: 10.1164/ajrccm/140.1.95. [DOI] [PubMed] [Google Scholar]
  41. Rao C. D., Pech M., Robbins K. C., Aaronson S. A. The 5' untranslated sequence of the c-sis/platelet-derived growth factor 2 transcript is a potent translational inhibitor. Mol Cell Biol. 1988 Jan;8(1):284–292. doi: 10.1128/mcb.8.1.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rappolee D. A., Mark D., Banda M. J., Werb Z. Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. Science. 1988 Aug 5;241(4866):708–712. doi: 10.1126/science.3041594. [DOI] [PubMed] [Google Scholar]
  43. Roberts A. B., Sporn M. B., Assoian R. K., Smith J. M., Roche N. S., Wakefield L. M., Heine U. I., Liotta L. A., Falanga V., Kehrl J. H. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4167–4171. doi: 10.1073/pnas.83.12.4167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sassone-Corsi P., Lamph W. W., Kamps M., Verma I. M. fos-associated cellular p39 is related to nuclear transcription factor AP-1. Cell. 1988 Aug 12;54(4):553–560. doi: 10.1016/0092-8674(88)90077-3. [DOI] [PubMed] [Google Scholar]
  45. Sassone-Corsi P., Ransone L. J., Lamph W. W., Verma I. M. Direct interaction between fos and jun nuclear oncoproteins: role of the 'leucine zipper' domain. Nature. 1988 Dec 15;336(6200):692–695. doi: 10.1038/336692a0. [DOI] [PubMed] [Google Scholar]
  46. Schliwa M. Action of cytochalasin D on cytoskeletal networks. J Cell Biol. 1982 Jan;92(1):79–91. doi: 10.1083/jcb.92.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Setoyama C., Frunzio R., Liau G., Mudryj M., de Crombrugghe B. Transcriptional activation encoded by the v-fos gene. Proc Natl Acad Sci U S A. 1986 May;83(10):3213–3217. doi: 10.1073/pnas.83.10.3213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Shimokado K., Raines E. W., Madtes D. K., Barrett T. B., Benditt E. P., Ross R. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell. 1985 Nov;43(1):277–286. doi: 10.1016/0092-8674(85)90033-9. [DOI] [PubMed] [Google Scholar]
  49. Sporn M. B., Roberts A. B., Shull J. H., Smith J. M., Ward J. M., Sodek J. Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. Science. 1983 Mar 18;219(4590):1329–1331. doi: 10.1126/science.6572416. [DOI] [PubMed] [Google Scholar]
  50. Welch M. P., Odland G. F., Clark R. A. Temporal relationships of F-actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction. J Cell Biol. 1990 Jan;110(1):133–145. doi: 10.1083/jcb.110.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Werb Z., Tremble P. M., Behrendtsen O., Crowley E., Damsky C. H. Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol. 1989 Aug;109(2):877–889. doi: 10.1083/jcb.109.2.877. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES