Intestinal macrophages: differentiation and involvement in intestinal immunopathologies (original) (raw)
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Gut, 1995
Multinucleated giant cells are an important feature of the granulomatous reaction in Crohn's disease (CD) but their cellular origin is poorly understood. The aim of this study was to discover if intestinal macrophages are capable of generating multinucleated giant cells in vitro in response to cytokine stimulation. Human intestinal macrophages were isolated from the intestinal mucosa ofCD and uninflamed surgical specimens. Isolated macrophages were cultured in chamber slides with and without exposure to a panel of cytokines and cell activators. Cell fusion, multinucleated giant cells formation, and the expression of adhesion molecules were assessed at various time intervals. In contrast with the autologous peripheral monocytes cell fusion was very poor in cultures of control intestinal macrophages and virtually no multinucleated giant cells were seen. Control intestinal macrophages seemed to poorly express the adhesion molecules required for cell to cell adhesion and fusion, namely ICAM-1 and LFA-1. None of these functions was affected by the exposure to cytokines, including interferon y. In cultures of macrophages isolated from CD tissues multinucleated giant cell formation spontaneously occurred as early as three days and was not enhanced by the addition of cytokines. CD macrophages seemed to highly express both ICAM-1 and LFA-1. These data show that human intestinal macrophages are unable to form multinucleated giant cells in response to stimuli and support the concept that they are downregulated in a number of functions. The data also suggest that macrophages participating in the ganulomatous reaction in CD are recruited from the circulation.
Monocyte differentiation in intestine-like macrophage phenotype induced by epithelial cells
Journal of leukocyte biology, 2001
Macrophages in normal colonic mucosa show a specific and distinct phenotype with low expression of the typical monocyte/macrophage surface antigens CD14, CD16, and CD11b and T-cell costimulatory molecules. A method for the in vitro induction of a macrophage phenotype similar to this intestinal phenotype is presented. Multicellular spheroids (MCSs) of intestinal epithelial cell (IEC) and control cell lines were cocultured with elutriated monocytes. Surface antigen expression was analyzed by immunohistochemistry and flow cytometry. Interleukin (IL)-1beta mRNA was measured by quantitative PCR. Monocytes adhered and infiltrated the MCSs within 24 h. In the MCSs of all IEC lines, the typical monocyte/macrophage surface antigens CD14, CD16, CD11b, and CD11c, which are detectable after 24 h of coculture by immunohistochemistry and flow cytometry, were down-regulated after 7 days (e.g., for CD14 at 24 h, expression was 86% of CD33+ cells; at day 7, it was 11%). A clear decrease of lipopolys...
Gut, 1994
Mucosal specimens from active Crohn's disease (ileum, n=6; colon, n=6), active ulcerative colitis (n=9), normal ileum (n=6), and normal colon (n=6) were subjected to paired immunofluorescence staining for characterisation of macrophage subsets in situ. In the normal state, only few CD68+ macrophages (<10%) expressing the myelomonocytic LI antigen (calprotectin) were seen. In inflamed mucosa, especially near small vessels, the CD68+L1+ fraction increased with the degree of inflammation, near ulcers to median 65% (range 35-91%). Cells reactive with the monoclonal antibody RFD7 were also increased in inflammation but less than 5% of them costained for LI antigen. It is concluded that LI producing macrophages are distinct from the RFD7+ subset and probably recently recruited from peripheral blood monocytes. Like granulocytes, L1+ macrophages may be important in non-specific defence, providing calprotectin with putative anti-microbial and anti-proliferative properties.
Intestinal Macrophages and Intestinal Infection
Biosciences Biotechnology Research Asia, 2021
There has been increased interest in the role played by macrophages in the maintenance of an active immune system and intestinal homeostasis. Nonetheless, they are also responsible for the rise of chronic pathologies such as inflammatory bowel syndrome in the gut. The lack of differentiation of monocytes in the intestines due to disease conditions leads to a fall in the diversity of microbiota and subsequent gut inflammation. Macrophages play a central role in the homeostasis and immunity of the gut, making them potential sources of novel therapies or remedies for inflammatory bowel disease (IBD) patients. To explore this possibility, this research discusses their structure, differentiation, and functionality in an in-depth manner. It will also describe their role in the local intestinal environment and how it changes upon infection. Finally, the paper will outline its conclusions as well as comment on the future outlook of related research.
Nature Communications, 2019
Bone marrow-derived circulating monocytes contribute to the replenishment and maintenance of the intestinal macrophage population. Intestinal monocytes undergo contextdependent phenotypic and functional adaptations to either maintain local immune balance or support intestinal inflammation. Here we use monocyte adoptive transfer to dissect the dynamics of monocyte-to-macrophage differentiation in normal and inflamed small intestine. We find that during homeostasis CCR2 and β7-integrin mediate constitutive homing of monocytes to the gut. By contrast, intestinal inflammation increases monocyte recruitment via CCR2, but not β7-integrin. In the non-inflamed intestine, monocytes gradually differentiate to express genes typically associated with tolerogenic macrophage functions. Conversely, immediately upon entry into the inflamed intestine, monocytes adapt a different expression pattern in a partly Trem-1-dependent manner. Our observations suggest that inflammation fundamentally changes the kinetics and modalities of monocyte differentiation in tissues.
Adaptations of intestinal macrophages to an antigen-rich environment
Seminars in Immunology, 2007
Intestinal macrophages, preferentially located in the subepithelial lamina propria, represent in humans the largest pool of tissue macrophages. To comply with their main task, i.e. the efficient removal of microbes and particulate matter that might have gained access to the mucosa from the intestinal lumen while maintaining local tissue homeostasis, several phenotypic and functional adaptations evolved. Most notably, microbeassociated molecular pattern (MAMP) receptors, including the lipopolysaccharide receptors CD14 and TLR4, but also the Fc receptors for IgA and IgG are absent on most intestinal Mø. Here we review recent findings on the phenotypic and functional adaptations of intestinal Mø and their implications for the pathogenesis of inflammatory bowel diseases.
American Journal of Respiratory Cell and Molecular Biology, 2015
Macrophages are dynamic cells that mature under the influence of signals from the local microenvironment into either classically (M1) or alternatively (M2) activated macrophages with specific functional and phenotypic properties. Although the phenotypic identification of M1 and M2 macrophages is well established in mice, this is less clear for human macrophages. In addition, the persistence and reversibility of polarized human phenotypes is not well established. Human peripheral blood monocytes were differentiated into uncommitted macrophages (M0) and then polarized to M1 and M2 phenotypes using LPS/IFN-g and IL-4/IL-13, respectively. M1 and M2 were identified as CD64 1 CD80 1 and CD11b 1 CD209 1 , respectively, by flow cytometry. Polarized M1 cells secreted IP-10, IFN-g, IL-8, TNF-a, IL-1b, and RANTES, whereas M2 cells secreted IL-13, CCL17, and CCL18. Functionally, M2 cells were highly endocytic. In cytokine-deficient medium, the polarized macrophages reverted back to the M0 state within 12 days. If previously polarized macrophages were given the alternative polarizing stimulus after 6 days of resting in cytokine-deficient medium, a switch in polarization was seen (i.e., M1 macrophages switched to M2 and expressed CD11b 1 CD209 1 and vice versa). In summary, we report phenotypic identification of human M1 and M2 macrophages, their functional characteristics, and their ability to be reprogrammed given the appropriate stimuli.