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Mesangial cell accessory functions: mediation by intercellular adhesion molecule-1
D C Brennan1, A M Jevnikar, F Takei
1Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital Boston, Massachusetts.
Abstract:
Mesangial cell (MC) proliferation is an early pathologic alteration characteristic of many forms of immune mediated glomerulonephritis. The intracapillary position, contractile capacity, and production of cytokines and other inflammatory molecules place MC in a pivotal position to initiate, mediate, and direct glomerular damage. We as well as others have noted increased levels of cytokines including IFN gamma, TNF, and IL-1 and the cell surface MHC class II and ICAM-1 molecules in the kidneys of mice with lupus nephritis. MHC class II and ICAM-1 molecules are central to the interaction of T cells with antigen presenting cells (APC). Since cytokines can increase both MHC class II and ICAM-1 molecules, we investigated whether mesangial cells could function as APC or accessory cells after cytokine stimulation. For these studies we established a permanent MC line through transformation with origin-deficient SV40 DNA. Surface expression of ICAM-1 was similar in untransformed MC as well as SV40 transformed MC from normal mice and in untransformed cells from mice with lupus nephritis. Basal expression of ICAM-1 was upregulated rapidly by IFN gamma, TNF, and IL-1. MHC class II expression could not be induced with TNF or IL-1 alone but required prolonged stimulation with IFN gamma. MC adhered and presented antigen to an antigen specific IaK restricted T cell hybridoma. Anti-ICAM-1 mAb decreased adhesion and antigen presentation of cytokine stimulated MC. By comparison, MHC class II mAb abrogated antigen presentation by MC bearing MHC class II but did not block adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Mesangial cells (MCs) can act as antigen-presenting cells (APCs) in glomerulonephritis. Cytokine stimulation enhances their ability to present antigens, contributing to kidney inflammation and damage.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Mesangial cell (MC) proliferation is a key feature of immune-mediated glomerulonephritis.
- MC position and inflammatory molecule production suggest a role in initiating glomerular damage.
- Increased cytokines, MHC class II, and ICAM-1 are observed in lupus nephritis.
Purpose of the Study:
- To investigate if mesangial cells can function as antigen-presenting cells (APCs) or accessory cells after cytokine stimulation.
- To determine the role of cytokines like IFN-gamma, TNF, and IL-1 in modulating MCs' APC capabilities.
Main Methods:
- Established a permanent mesangial cell (MC) line using SV40 DNA transformation.
- Analyzed surface expression of ICAM-1 and MHC class II molecules on MCs.
- Stimulated MCs with cytokines (IFN-gamma, TNF, IL-1) and assessed antigen presentation to T cell hybridomas.
- Utilized monoclonal antibodies (mAbs) against ICAM-1 and MHC class II to block cellular interactions.
Main Results:
- Intercellular Adhesion Molecule 1 (ICAM-1) expression was upregulated by IFN-gamma, TNF, and IL-1.
- Major Histocompatibility Complex (MHC) class II expression required prolonged IFN-gamma stimulation.
- Cytokine-stimulated MCs adhered to and presented antigens to T cells.
- Anti-ICAM-1 mAb reduced MC adhesion and antigen presentation; anti-MHC class II mAb blocked antigen presentation but not adhesion.
Conclusions:
- Mesangial cells can be induced to function as antigen-presenting cells (APCs) by specific cytokines.
- Both ICAM-1 and MHC class II expression are crucial for MC-mediated antigen presentation.
- These findings highlight MCs as potential key players in the immune response within the glomerulus.