Expression, regulation and functional activities of aminopeptidase N (EC 3.4.11.2; APN; CD13) on murine macrophage J774 cell line.
Aminopeptidase N (APN; CD13) is a ubiquitous membrane-bound enzyme. Expressed on haematopoietic cells APN participates in inflammatory and immune responses by regulating local concentration of chemotactic peptides and by fine-tuning antigen presentation. The data of this study have shown for the first time that cells of murine macrophage line, J774, often used as a model cell line, express CD13 both at transcriptional level and at the level of membrane protein with aminopeptidase N (APN) activity. The level of transcriptional expression of CD13/APN on J774 cells was compared to that found on normal cells participating in immune responses. The highest CD13/APN level was found in peritoneal macrophages, followed by J774 cells and splenocytes, whereas lymph node, thymus and bone-marrow cells expressed low level of CD13/APN mRNA. Further, the CD13 (mRNA, protein and APN) on J774 cells could be up-regulated by pro-inflammatory IFN-γ which is in agreement with the known role of CD13/APN in inflammatory responses. Co-regulation of CD13 with MHC-II and CD86 is in line with the reported role of APN expressed on human cells in antigen presentation. CD13 on J774 cells co-localize with mannose receptors (MR), and co-internalize upon MR ligation by ovalbumin, suggesting a new function of CD13 in MR-mediated phagocytosis. That function of CD13 is independent of APN enzyme activity. Anti-inflammatory drug dexamethasone diminished the IFN-γ-induced increase of CD13. The observed down-regulation of CD13 on J774 cells by dexamethasone might be relevant as a possible mechanism involved in action of anti-inflammatory drugs on normal macrophages.
Gabrilovac
Jelka
J
Division of Molecular Medicine, Laboratory for Experimental Haematology, Immunology and Oncology, Ruđer Bošković Institute, Zagreb, Croatia. gabril@irb.hr
Cupić
Barbara
B
Zivković
Emilija
E
Horvat
Lucija
L
Majhen
Dragomira
D
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D018826:CD13 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism*
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D003907:Dexamethasone; D007371:Interferon-gamma; D018826:CD13 Antigens