Expression of MRP8 and MRP14 by macrophages is a marker for severe forms of glomerulonephritis

Abstract

Expression of two S100 proteins, myeloid related protein (MRP)8 and MRP14, as well as their complex formation indicate proinflammatory properties of macrophages. We analyzed if the different forms of glomerulonephritis (GN) are associated with the appearance of certain phenotypes of infiltrating macrophages characterized by expression of MRP8 and MRP14 as well as their complex formation. Immunohistochemical analysis of 89 renal biopsies with different forms of nephritis revealed that expression and complex formation of MRP8 and MRP14 by infiltrating macrophages in the glomeruli correlated with the severity of the inflammatory process. As such, MRP8/MRP14-expressing monocytes prevailed in highly proliferating forms of GN, i.e., systemic lupus erythematosus GN and extracapillary GN. In contrast, a high percentage of macrophages in the renal interstitium expressed MRP8 and MRP14 without concomitant formation of their complex, and they indicated a chronic type of inflammatory reaction in GN. Immunosuppressive drugs had no direct effects on the expression of MRP8 and MRP14 in macrophages in vitro. The correlation of MRP8 and MRP14 expression with disease activity indicates that these calcium-binding proteins are of pathophysiological relevance in GN. In addition, our findings reflect differences in the inflammatory mechanisms underlying the various forms of GN, as they revealed that distinct macrophage subpopulations prevail in the different forms of GN.