Aminopeptidase N (CD13) functionally interacts with FcγRs 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 (FcγRs) has been proposed. In this work, we evaluated possible functional interactions between CD13 and FcγRs in human peripheral blood monocytes and in U-937 promonocytic cells. Our results show that during FcγR-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 FcγRI and CD13 are ingested simultaneously, more efficiently than those that interact through the FcγRI only. Also, co-cross-linking of CD13 with FcγRI by specific mAbs increases the level and duration of Syk phosphorylation induced by FcγRI cross-linking. Finally, FcγRI and CD13 colocalize in zones of cellular polarization and coredistribute after aggregation of either of them. These results demonstrate that CD13 and FcγRI can functionally interact on the monocytic cell membrane and suggest that CD13 may act as a signal regulator of FcγR function.