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The macrophage system in the intestinal muscularis externa during inflammation: an immunohistochemical and quantitative study of osteopetrotic mice

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Abstract

Intestinal inflammation results in disturbed intestinal motility in humans as well as in animal models. This altered function of smooth muscle cells and/or the enteric nervous system may be caused by activation of macrophages in muscularis externa and a thereby following release of cytokines and chemokines that causes influx of mononuclear cells and neutrophilic granulocytes. We subjected osteopetrotic (op/op) mice that lack certain macrophage subtypes, e.g. macrophages in the muscularis externa and +/+ mice to LPS to induce inflammatory cell influx. The densities of F4/80+, MHCII+, and myeloperoxidase+ cells were quantified using stereological sampling. In +/+ mice we found that MHCII+ cells outnumber F4/80+ cells and that LPS injection increased the density of MHCII+ cells temporarily but not that of F4/80+ cells. This indicates that an upregulation of MHCII antigen takes place and that two or more macrophage subtypes with comparable morphologies exist. Osteopetrotic mice lacked MHCII+, CD169+, and F4/80+ cells after either treatment, which indicate that these cells are CSF-1-dependent. LPS induced VCAM-1 activation of the vessels, modest influx of granulocytes, as well as an iNOS-activation in a cell type different from macrophages in both +/+ and op/op mice.

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Acknowledgments

The present study was supported by a grant from S.C.E. Friis and wife D. Friis’s Foundation. The authors wish to thank Ha Nguyen, Pernille Froh and Keld Ottesen for skilled technical assistance.

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Authors and Affiliations

  1. Department of Cellular and Molecular Medicine, The Panum Building, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark

    H. B. Mikkelsen & H. Hadberg

  2. Department of Neuroscience and Pharmacology, The Panum Building, Faculty of Health Sciences, University of Copenhagen, Copenhagen N, Denmark

    J. O. Larsen

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  1. H. B. Mikkelsen
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  3. H. Hadberg
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Correspondence to H. B. Mikkelsen.

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Mikkelsen, H.B., Larsen, J.O. & Hadberg, H. The macrophage system in the intestinal muscularis externa during inflammation: an immunohistochemical and quantitative study of osteopetrotic mice. Histochem Cell Biol 130, 363–373 (2008). https://doi.org/10.1007/s00418-008-0423-x

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  • DOI: https://doi.org/10.1007/s00418-008-0423-x

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