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Monocyte chemoattractant protein-1 (MCP-1) inhibits the intestinal-like differentiation of monocytes

  1. T. Spoettl,
  2. M. Hausmann,
  3. M. Herlyn,
  4. M. Gunckel,
  5. A. Dirmeier,
  6. W. Falk,
  7. H. Herfarth,
  8. J. Schoelmerich,
  9. G. Rogler

Article first published online: 1 JUN 2006

DOI: 10.1111/j.1365-2249.2006.03113.x

Issue

Clinical & Experimental Immunology

Clinical & Experimental Immunology

Volume 145, Issue 1, pages 190–199, July 2006

Additional Information

How to Cite

Spoettl, T., Hausmann, M., Herlyn, M., Gunckel, M., Dirmeier, A., Falk, W., Herfarth, H., Schoelmerich, J. and Rogler, G. (2006), Monocyte chemoattractant protein-1 (MCP-1) inhibits the intestinal-like differentiation of monocytes. Clinical & Experimental Immunology, 145: 190–199. doi: 10.1111/j.1365-2249.2006.03113.x

Author Information

  1. Department of Internal Medicine I, University of Regensburg, Germany, and The Wistar Institue, University of Pennsylvania, Philadelphia, PA, USA

*Gerhard Rogler MD, PhD, Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany. E-mail: gerhard.rogler@klinik.uni-regensburg.de

Publication History

  1. Issue published online: 1 JUN 2006
  2. Article first published online: 1 JUN 2006
  3. Accepted for publication 20 April 2006

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Keywords:

  • MCP-1;
  • intestinal macrophages;
  • multicellular spheroids;
  • differentiation;
  • inflammatory bowel disease

Summary

Monocytes (MO) migrating into normal, non-inflamed intestinal mucosa undergo a specific differentiation resulting in a non-reactive, tolerogenic intestinal macrophage (IMAC). Recently we demonstrated the differentiation of MO into an intestinal-like macrophage (MAC) phenotype in vitro in a three-dimensional cell culture model (multi-cellular spheroid or MCS model). In the mucosa of patients with inflammatory bowel disease (IBD) in addition to normal IMAC, a reactive MAC population as well as increased levels of monocyte chemoattractant protein 1 (MCP-1) is found. The aim of this study was to investigate the influence of MCP-1 on the differentiation of MO into IMAC. MCS were generated from adenovirally transfected HT-29 cells overexpressing MCP-1, macrophage inflammatory protein 3 alpha (MIP-3α) or non-transfected controls and co-cultured with freshly elutriated blood MO. After 7 days of co-culture MCS were harvested, and expression of the surface antigens CD33 and CD14 as well as the intracellular MAC marker CD68 was determined by flow-cytometry or immunohistochemistry. MCP-1 and MIP-3α expression by HT-29 cells in the MCS was increased by transfection at the time of MCS formation. In contrast to MIP-3α, MCP-1 overexpression induced a massive migration of MO into the three-dimensional aggregates. Differentiation of IMAC was disturbed in MCP-1-transfected MCS compared to experiments with non-transfected control aggregates, or the MIP-3α-transfected MCS, as indicated by high CD14 expression of MO/IMAC cultured inside the MCP-1-transfected MCS, as shown by immunohistochemistry and FACS analysis. Neutralization of MCP-1 was followed by an almost complete absence of monocyte migration into the MCS. MCP-1 induced migration of MO into three-dimensional spheroids generated from HT-29 cells and inhibited intestinal-like differentiation of blood MO into IMAC. It may be speculated that MCP-1 could play a role in the disturbed IMAC differentiation in IBD mucosa.

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