Spoettl, T. and Hausmann, M. and Herlyn, M. and Gunckel, M. and Dirmeier, A. and Falk, W. and Herfarth, H. and Schoelmerich, J. and Rogler, Gerhard (2006) Monocyte chemoattractant protein-1 (MCP-1) inhibits the intestinal-like differentiation of monocytes. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 145 (1). pp. 190-199. ISSN 0009-9104, 1365-2249
Full text not available from this repository. (Request a copy)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-3 alpha) 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-3 alpha expression by HT-29 cells in the MCS was increased by transfection at the time of MCS formation. In contrast to MIP-3 alpha, 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-3 alpha-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; EPITHELIAL-CELLS; CROHNS-DISEASE; MACROPHAGE DIFFERENTIATION; COLONIC MACROPHAGES; MUCOSAL MACROPHAGES; UP-REGULATION; EXPRESSION; PHENOTYPE; MCP-1; intestinal macrophages; multicellular spheroids; differentiation; inflammatory bowel disease |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Feb 2021 10:48 |
| Last Modified: | 10 Feb 2021 10:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34333 |
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