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Modulation of the expression of M150 on macrophages by Th1/Th2 cytokines and co-stimulatory molecules CD40, B7-1,
S Suvas1, H Vohra, J N Agrewala
1Immunology Laboratory, Institute of Microbial Technology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract:
M150 is an 150-kDa protein associated with the surface of macrophages and is responsible chiefly for the activation of Th1 cells. It is a unique subset of the lysosome-associated membrane protein-1 glycoprotein and its co-stimulatory activity depends on its post-translational modification, which has a distinct glycosylation pattern restricted to macrophages. In the present study, we have observed that M150 is expressed constitutively on peritoneal but not splenic macrophages isolated from mice of different genetic backgrounds: Balb/c, C57BL/6 and C3He. However, M150 was expressed not only on peritoneal but also on splenic macrophages of non-obese diabetic (NOD) mice. Expression on splenic macrophages was induced by culture with lipopolysaccharide (LPS). Expression could also be significantly up-regulated by interferon (IFN)-gamma and granulocyte-macrophage colony stimulating factor (GM-CSF) but was inhibited by interleukin (IL)-10; IL-4 exhibited no effect. Further, cross-linking of B7-2, CD40, ICAM-1 but not B7-1 enhanced the level of M150 significantly. IFN-gamma and GM-CSF acted synergistically with CD40. The significance of these findings is that cytokines IFN-gamma, GM-CSF and IL-10 and the co-stimulatory molecules B7-2, CD40 and ICAM-1 can regulate the expression of M150 on macrophages.
Insights
M150 protein activates Th1 cells and its expression on macrophages is regulated by cytokines like interferon-gamma and granulocyte-macrophage colony stimulating factor, and co-stimulatory molecules.
Area of Science:
- Immunology
- Cell Biology
- Glycoprotein Research
Background:
- M150 is a 150-kDa macrophage surface protein crucial for Th1 cell activation.
- Its co-stimulatory activity is linked to post-translational modification and a unique macrophage-specific glycosylation pattern.
Purpose of the Study:
- To investigate the expression patterns of M150 on macrophages from different mouse strains.
- To determine the regulatory effects of cytokines and co-stimulatory molecules on M150 expression.
Main Methods:
- Isolation and analysis of peritoneal and splenic macrophages from Balb/c, C57BL/6, C3He, and non-obese diabetic (NOD) mice.
- Culture of macrophages with lipopolysaccharide (LPS), cytokines (IFN-gamma, GM-CSF, IL-10, IL-4), and cross-linking of co-stimulatory molecules (B7-2, CD40, ICAM-1, B7-1).
Main Results:
- M150 is constitutively expressed on peritoneal macrophages but not splenic macrophages in most strains.
- NOD mice exhibit M150 expression on both peritoneal and splenic macrophages.
- LPS, IFN-gamma, and GM-CSF induce/up-regulate M150 expression; IL-10 inhibits it.
- Cross-linking of B7-2, CD40, and ICAM-1 enhances M150 levels, with synergistic effects observed for IFN-gamma and GM-CSF with CD40.
Conclusions:
- Cytokines (IFN-gamma, GM-CSF, IL-10) and co-stimulatory molecules (B7-2, CD40, ICAM-1) play significant roles in regulating M150 expression on macrophages.
- These findings highlight the intricate control mechanisms governing M150 function in immune responses.
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