The Journal of Immunology, 2006, 177: 1377.
Copyright © 2006 by The American Association of Immunologists
Comment on "Mast Cell-Mediated Remodeling and Fibrinolytic Activity Protect against Fatal Glomerulonephritis"
Kathrin Hochegger*,
Alexander R. Rosenkranz*,
Frank Siebenhaar
and
Marcus Maurer
* Medical University Innsbruck Clinical Division of Nephrology Innsbruck, Austria
Department of Dermatology and Allergy Charité–Universitätsmedizin Berlin Berlin, Germany
Recently, Kanamaru et al. (1) reported that mast cells (MCs) protect from murine anti-glomerular basement membrane (GBM) glomerulonephritis (GN). The results of their experiments are very similar to those we first reported in 2005 (2). While we are pleased that the unexpected findings from our study were independently confirmed, we are concerned with the conclusions drawn. Our results led us to conclude that MCs exert their protective role in anti-GBM-GN by immunomodulatory effects rather than acting as effector cells. This view is supported by i) increased MC numbers in the draining lymph nodes after inducing anti-GBM-GN (2), ii) the critical role of MCs in limiting the recruitment of T cells to inflamed kidneys (2), and iii) by our recent report showing that CD4+CD25+ T cells localized in the draining lymph nodes can also inhibit anti-GBM-GN (3). In contrast, Kanamaru et al. (1) speculate that MCs are protective in anti-GBM-GN "by their ability to mediate remodelling and repair functions," a hypothesis based on the demonstration that MC-deficient KitW/KitW-v mice exhibit increased fibrin depositions and decreased plasminogen activator activity. We suspect that these observations are the result, rather than the cause, of the increased glomerular inflammatory activity seen in these mice. For example, anti-GBM-GN in P-selectin-deficient mice, which have regular numbers of MCs and intact MC function, is also associated with dramatic increases of fibrin deposition and glomerular damage (4). Taken together, we feel that the evidence presently available indicates that MCs control anti-GBM-GN pathogenesis via their immunomodulatory effects.
References
- Kanamaru, Y., L. Scandiuzzi, M. Essig, C. Brochetta, C. Guérin-Marchand, Y. Tomino, R. C. Monteiro, M. Peuchmaur, U. Blank. 2006. Mast cell-mediated remodeling and fibrinolytic activity protect against fatal glomerulonephritis. J. Immunol. 176: 5607-5615. [Abstract/Free Full Text]
- Hochegger, K., F. Siebenhaar, V. Vielhauer, D. Heininger, T. N. Mayadas, G. Mayer, M. Maurer, A. R. Rosenkranz. 2005. Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritis. Eur. J. Immunol. 35: 3074-3082. [Medline]
- Wolf, D., K. Hochegger, A. M. Wolf, H. F. Rumpold, G. Gastl, H. Tilg, G. Mayer, E. Gunsilius, A. R. Rosenkranz. 2005. CD4+CD25+ regulatory T cells inhibit experimental anti-glomerular basement membrane glomerulonephritis in mice. J. Am. Soc. Nephrol. 16: 1360-1370. [Abstract/Free Full Text]
- Rosenkranz, A. R., D. L. Mendrick, R. S. Cotran, T. N. Mayadas. 1999. P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation. J. Clin. Invest. 103: 649-659. [Medline]
