EXPRESSION AND COMPLEX-FORMATION OF S100-LIKE PROTEINS MRP8 AND MRP14BY MACROPHAGES DURING RENAL-ALLOGRAFT REJECTION

MRPS and MRP14, two S100-like calcium-binding proteins, are expressed during differentiation of monocytes/macrophages. Both assemble to diff erent noncovalently associated complexes that are supposed to represen t the biologically active states. The present study was intended to in vestigate the molecular basis of macrophage heterogeneity with respect to expression and complex formation of MRP8 and MRP14 during acute an d chronic rejection of renal allografts. First, specificity of antiser a and mAbs to be directed against MRP8, MRP14, or MRP8/MRP14 heterodim ers was determined by immunocytochemical and Western blot analyses of L132 fibroblasts (co-)transfected with MRP8 and/or MRP14 cDNA Then, im munohistochemical analysis of biopsy specimens obtained from kidney al lografts after acute rejection was performed, revealing a parallel exp ression of MRPS and MRP14 with coincident MRP8/MRP14 heterodimer forma tion in infiltrating monocytes. In contrast, chronic allograft rejecti on was characterized by a subpopulation of monocytes defined by the ab sence of MRP8/MRP14 complex formation despite expression of MRPS and M RP14 monomers. Double-labeling experiments showed that this was due in part to differential expression of MRPS and MRP14 in infiltrate macro phages of chronic rejection. The data presented demonstrate for the fi rst time differences in MRP8/MRP14 complex assembly by infiltrating mo nocytes in situ. These seem to be of pathophysiological relevance sinc e complex formation defines subpopulations of monocytes associated wit h distinct pathways of immunological reactions. Differences in the mod e of calcium-dependent signaling may, therefore, be of importance for understanding the molecular basis of macrophage heterogeneity during a cute and chronic allograft rejection.