title: Aminopeptidase N (CD13) functionally interacts with FcgammaRs in human monocytes.
abstract: Aminopeptidase N (E.C. 3.4.11.2) is a membrane-bound metalloproteinase expressed in many tissues. Although its cytoplasmic portion has only eight amino acids, cross-linking of CD13 by monoclonal antibodies (mAb) has been shown to trigger intracellular signaling. A functional association between CD13 and receptors for immunoglobulin G (FcgammaRs) has been proposed. In this work, we evaluated possible functional interactions between CD13 and FcgammaRs in human peripheral blood monocytes and in U-937 promonocytic cells. Our results show that during FcgammaR-mediated phagocytosis, CD13 redistributes to the phagocytic cup and is internalized into the phagosomes. Moreover, modified erythrocytes that interact with the monocytic cell membrane through FcgammaRI and CD13 are ingested simultaneously, more efficiently than those that interact through the FcgammaRI only. Also, co-cross-linking of CD13 with FcgammaRI by specific mAbs increases the level and duration of Syk phosphorylation induced by FcgammaRI cross-linking. Finally, FcgammaRI and CD13 colocalize in zones of cellular polarization and coredistribute after aggregation of either of them. These results demonstrate that CD13 and FcgammaRI can functionally interact on the monocytic cell membrane and suggest that CD13 may act as a signal regulator of FcgammaR function.
authors.affiliation: Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México.
authors.forename: Paola
authors.initials: P
authors.lastname: Mina-Osorio
authors.forename: Enrique
authors.initials: E
authors.lastname: Ortega
mesh_terms: D018826:CD13 Antigens / Q000032:analysis / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009000:Monocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D020298:U937 Cells
chemical_list: D004792:Enzyme Precursors; C489017:FCGR1A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D018826:CD13 Antigens