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The clinical investigator

, Volume 70, Issue 9, pp 825–842 | Cite as

The inflammatory function of renal glomerular mesangial cells and their interaction with the cellular immune system

  • H. H. Radeke
  • K. Resch
Guest Lecture, “Gsellschaft für Nephrologie”, 23rd Congress

Summary

The autoimmune nature of chronic progredient glomerular diseases has been well established. Like in other chronic inflammatory diseases, the active role of organ-borne cells has become increasingly apparent — both for the inflammatory process and for the initiation and perpetuation of the immune reaction. In most forms of glomerulonephritis, intrinsic glomerular mesangial cells are likely candidates to come into intimate contact with immune cells such as monocytes or lymphocytes. On the basis of cell culture studies we would like to integrate the current knowledge available about the responsiveness of mesangial cells to inflammatory agents and the resulting secretory capacity and, moreover, their possible role in sustaining chronic inflammatory injury and autoimmune reactions through a direct interaction with lymphocytes. Apart from being responsive to physiological stimuli such as angiotensin II, glomerular mesangial cells are predominantly activated by agents related to inflammation. This includes exogenous substances such as the components of gram-negative bacteria and an array of highly potent immunological stimuli like antigen-antibody complexes, activated complement, or various cytokines. The transformation of resting mesangial cells to proliferating cells with an accompanying expansion of their secretory profile and responsiveness is due to mediators like platelet-derived growth factor, transforming growth factor, and others. Numerous low-molecular-weight substances (O2, H2O2, NO, platelet-activating factor, eicosanoids), proteins (proteinases, matrix components, interleukins 1 and 6, colony-stimulating factors, growth factors), and cell-surface molecules released or expressed by mesangial cells participate in the inflammatory process. Among these products interleukin 1 and/or 6, class II major histocompatibility antigen and integrins also support an interaction with the cellular immune system. It has been well documented that mesangial cells induced in vitro by recombinant T-cell lymphokines, such as interferon-γ, do express MHC II and ICAM-1 and could function as antigen-presenting cells. However, and perhaps more interestingly, our own recent experiments with cocultures of syngeneic mouse lymphocytes and mesangial cells have demonstrated that T-cells are directly activated by cultured mesangial cells, thus resembling a mesangial cell-specific autoimmune reaction. In parallel to clinical studies searching for a mesangial autoantigen these experiments might help to elucidate the mechanisms of initiation and perpetuation of mesangial cell-dependent autoimmune glomerulonephritis.

Key words

Glomerular mesangial cell Glomerulonephritis Cytokines T-lymphocytes 

Abbreviations

MC

glomerular mesangial cell

GN

glomerulonephritis

GBM

glomerular basement membrane

MHC II

class II major histocompatibility antigen

CSF

colony stimulating factor

LN

lymphnode lymphocyte

HETE

hydroxyeicosatetraenoic acid

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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • H. H. Radeke
    • 1
  • K. Resch
    • 1
  1. 1.Medizinische Hochschule HannoverInstitut für MolekularpharmakologieHannover 61Germany

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