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Interleukin 4 potently enhances murine macrophage mannose receptor activity: A marker of alternative immunologic macrophage activation
Open accessAbstract
Expression of the macrophage mannose receptor is inhibited by interferon gamma (IFN-gamma), a T helper type 1 (Th-1)-derived lymphokine. Interleukin 4 (IL-4), a Th-2 lymphocyte product, upregulates major histocompatibility class II antigen expression but inhibits inflammatory cytokine production by macrophages. We have studied the effect of IL-4 on expression of the macrophage mannose receptor (MMR) by elicited peritoneal macrophages. We found that recombinant murine IL-4 enhances MMR surface expression (10-fold) and activity (15-fold), as measured by the respective binding and degradation of 125I-mannose-bovine serum albumin. Polymerase chain reaction analysis of cDNAs from purified primary macrophage populations revealed that MMR, but not lysozyme or tumor necrosis factor alpha, mRNA levels were markedly increased by IL-4. The above effects were associated with morphologic changes. These data establish IL-4 as a potent and selective enhancer of murine MMR activity in vitro. IL-4 induces inflammatory macrophages to adopt an alternative activation phenotype, distinct from that induced by IFN-gamma, characterized by a high capacity for endocytic clearance of mannosylated ligands, enhanced (albeit restricted) MHC class II antigen expression, and reduced proinflammatory cytokine secretion.
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“Alternatively activated macrophages are stimulated by IL-4, IL-13 and glucocorticoids, inhibit pro-inflammatory cytokines, promote anti-inflammatory cytokines, and upregulate mannose receptors.[123, 124]”
From Foreign body reaction to biomaterials (2008) · cites this paper as [123]
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“Later during the healing process, macrophages transit from a pro-inflammatory M1 to a reparative M2 phenotype, expressing anti-inflammatory mediators, e.g., IL-1R antagonist, decoy IL-1 receptor type II and IL-10, and growth factors, e.g., TGFβ, VEGF and IGF1, promoting fibroblast proliferation, ECM synthesis and angiogenesis (Fig. 2) [59, 60].”
From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [60]
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“A phenotypic switch in biomaterial adherent macrophages to a more alternatively activated macrophage phenotype over time is expected because in order to induce fusion IL-4 is added to our culture system on days 3 and 7[58] IL-4 is known to induce an alternative activation phenotype in macrophages inclusive of the upregulation of mannose receptors[123] which has been found to be necessary for the”
From Foreign body reaction to biomaterials (2008) · cites this paper as [123]
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“Alternatively activated macrophages do not require any priming, because interleukins IL-4 and/or IL-13 can act as enough stimuli [190,191].”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [190]
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Metadata
- Authors
- Stein, M., Keshav, S., Harris, N., & Gordon, S.
- Affiliations
- University of Oxford (GB)
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1992-07-01
- Volume
- 176
- Issue
- 1
- Pages
- 287-292
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2119288
- OpenAlex
- W2123640179
- Cited by
- 1,960
- References
- 21
- Citations by year
- 2026: 48 · 2025: 66 · 2024: 74 · 2023: 80 · 2022: 115 · 2021: 102 · 2020: 92 · 2019: 93 · 2018: 94 · 2017: 106 · 2016: 116 · 2015: 110 · 2014: 137 · 2013: 100 · 2012: 88
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- IL-4, CD206, alternative macrophage activation, interferon-gamma, peritoneal macrophages, mannose binding, MHC class II antigen expression, proinflammatory cytokine secretion
- MeSH terms
- Mannose Receptor, Animals, Base Sequence, Interferon-gamma, Macrophage Activation, Macrophages, Male, Mannose, Mice, Inbred BALB C, Molecular Sequence Data, Receptors, Cell Surface, Receptors, Immunologic, RNA, Messenger, Interleukin-4, Lectins, C-Type, Mannose-Binding Lectins, Mice
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