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Monocyte chemoattractant protein-1 (MCP-1) inhibits the intestinal-like differentiation of monocytes.
- Source :
-
Clinical & Experimental Immunology . Jul2006, Vol. 145 Issue 1, p190-199. 10p. 1 Diagram, 6 Graphs. - Publication Year :
- 2006
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00099104
- Volume :
- 145
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Clinical & Experimental Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 21153792
- Full Text :
- https://doi.org/10.1111/j.1365-2249.2006.03113.x