The membrane-bound ectopeptidase CPM as a marker of macrophage maturation in vitro and in vivo.
During terminal maturation of human blood monocytes into macrophages, a multitude of phenotypic and functional changes occurs: cells increase in size, they enhance their capacity for phagocytosis and tumor cytotoxicity but decrease their ability for T-lymphocyte stimulation. The pattern of secreted cytokines is shifted as is the profile of surface antigens. We recently identified carboxypeptidase M (CPM) as a macrophage maturation-associated antigen detected by mAb MAX. 1/MAX. 11. CPM, a phosphoinositol-linked ectopeptidase, is able to process a multitude of different substrates, among them immunologically important peptides like bradykinin, anaphylatoxins and enkephalins. It was previously shown to be expressed in placenta, lung, and kidney. CPM as detected by MAX. 1/11 shows a strong expression on monocyte-derived macrophages in vitro and on macrophages in vivo accompanying T-lymphocyte activation like during allogeneic transplant rejection or allergic alveolitis. In contrast, its expression is suppressed on macrophages by some types of tumor cells. CPM expression seems to correlate with macrophage cytotoxic functions. However, the biological importance of CPM expression in human macrophages in vivo is difficult to predict. A wide range of biologically active peptides are cleaved by CPM, and the relevance of CPM peptide processing during an immune reaction is only poorly understood. The generation and analysis of CPM-deficient animals might improve our understanding of CPM function. Therefore we cloned a cDNA for the murine homologue of CPM. However, expression of mCPM was undetectable in murine primary macrophages and macrophage cell-lines, suggesting that CPM expression and function is not conserved between human and mouse macrophages.
Rehli
M
M
Department of Hematology and Oncology, University of Regensburg, Germany.
Krause
S W
SW
Andreesen
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000032:analysis*; D000954:Antigens, Surface / Q000032:analysis; D015415:Biomarkers; D002454:Cell Differentiation; D002462:Cell Membrane / Q000201:enzymology*; D018076:DNA, Complementary / Q000235:genetics; D058851:GPI-Linked Proteins; D018390:Gene Targeting; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology / Q000201:enzymology*; D008565:Membrane Proteins / Q000032:analysis*; D008666:Metalloendopeptidases / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D009928:Organ Specificity; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015415:Biomarkers; D018076:DNA, Complementary; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; C058479:carboxypeptidase M; D008666:Metalloendopeptidases