CD13 mediates phagocytosis in human monocytic cells

Abstract

CD13 is a membrane-bound ectopeptidase, highly expressed on monocytes, macrophages, and dendritic cells. CD13 is involved in diverse functions, including degradation of peptide mediators, cellular adhesion, migration, viral endocytosis, signaling, and positive modulation of phagocytosis mediated by FcγRs and other phagocytic receptors. In this work, we explored whether besides acting as an accessory receptor, CD13 by itself is a primary phagocytic receptor. We found that hCD13 mediates efficient phagocytosis of large particles (erythrocytes) modified so as to interact with the cell only through CD13 in human macrophages and THP-1 monocytic cells. The extent of this phagocytosis is comparable with the phagocytosis mediated through the canonical phagocytic receptor FcγRI. Furthermore, we demonstrated that hCD13 expression in the nonphagocytic cell line HEK293 is sufficient to enable these cells to internalize particles bound through hCD13. CD13-mediated phagocytosis is independent of other phagocytic receptors, as it occurs in the absence of FcγRs, CR3, and most phagocytic receptors. Phagocytosis through CD13 is independent of its enzymatic activity but is dependent on actin rearrangement and activation of PI3K and is partially dependent on Syk activation. Moreover, the cross-linking of CD13 with antibodies rapidly induced pSyk in human macrophages. Finally, we observed that antibody-mediated cross-linking of hCD13, expressed in the murine macrophage-like J774 cell line, induces production of ROS. These results demonstrate that CD13 is a fully competent phagocytic receptor capable of mediating internalization of large particles.

Macrophage Polarization Modulates FcγR- and CD13-Mediated Phagocytosis and Reactive Oxygen Species Production, Independently of Receptor Membrane Expression

“…We used an experimental system to direct sheep erythrocytes (as the phagocytic prey) to individual receptors on the cell, as reported previously (14). Erythrocytes loaded with CFSE and labeled with biotin and streptavidin were coated with biotin-F(ab′)2 fragments of goat anti-mouse IgG (EBS-Fab).…”

“…Modified SRBCs were prepared as described previously (14). In brief, erythrocytes (at 1.2 × 10 9 /mL in PBS-BSA 0.1%) were stained with 10 mM CFSE.…”

“…For its part, CD13 is a membrane peptidase, which participates in a wide variety of functions (13). CD13 is highly expressed on myeloid cells, and we have recently shown that in human monocytes and macrophages, CD13 is a competent phagocytic receptor capable of mediating phagocytosis, independently of other receptors (14). CD13 can also modulate phagocytosis mediated by FcγRs (15) and by other receptors (16).…”

“…CD13 can also modulate phagocytosis mediated by FcγRs (15) and by other receptors (16). In addition, CD13 crosslinking induces ROS production in macrophages (14). …”

Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and lamininα1 expressing cells

“…In order to characterize this cell type, we performed immunohistochemistry of known markers. The cells that clustered at the calcified sites were uniformly positive for CD13, a marker of several cell types including: pericytes/perivascular cells that support vasculature and play a role in blood brain barrier permeability [26], mesenchymal stem cells proposed to regulate immunomodulating peptides as well as vasoactive and neuropeptide hormones [27], and pro-inflammatory monocytes mediating adhesion and phagocytosis [28,29] (Fig. 9B).…”