An interaction between CD16 and CR3 enhances iC3b binding to CR3 but is lost during differentiation of monocytes into dendritic cells

Abstract

The receptor for the iC3b fragment of complement, CR3, is involved in monocytes/macrophages and neutrophils phagocytosis. CR3 is known to interact with the low affinity receptor for Ig (CD16) and previous studies have suggested that this cooperation modulates CR3 functions. Herein we have studied the effect of CD16 on the ability of human monocytes CR3 to bind to iC3b. We show that iC3b binding to CR3 is inhibited by several reagents that are known to dissociate the CD16/CR3 complex. In addition, treatment of monocytes with soluble CD16 inhibited iC3b binding to CR3. Together, these data indicate that iC3b binding to monocyte CR3 is up-regulated by an interaction between membrane CD16 and CR3. The implication of CD16 in CR3 binding to iC3b was also analyzed after monocyte differentiation into dendritic cells (DC). Differentiation of monocytes into DC abrogates the cooperation between CD16 and CR3, due to a loss of CD16/CR3 interaction. In accordance, this phenomenon is associated with a lack of iC3b binding to DC. As a consequence, deposition of iC3b on apoptotic cells does not modify their phagocytosis by DC. In conclusion, we demonstrate a cooperation between CD16 and CR3 that favors iC3b binding to CR3 but is lost on DC.

Apoptotic Cell-Mediated Immunoregulation of Dendritic Cells Does Not Require iC3b Opsonization

“…These data, including our own, have mostly been generated using artificial means of activating CR3 to model the presumed effects of iC3b opsonized apoptotic cells binding to the receptor. Data examining the role of iC3b/CR3 interactions in the phagocytosis of apoptotic cells is conflicting (10,(12)(13)(14). In this report, we provide evidence suggesting that CR3 is not necessary for either apoptotic cell phagocytosis or apoptotic cell mediated DC cytokine suppression.…”

“…In vitro studies of serum opsonization have been limited to phagocytosis (10,(12)(13)(14) and offer conflicting reports. Apoptotic cells in serum-free conditions have been recently been shown to be equally effective as apoptotic cells with serum opsonins in their ability to inhibit LPS induced IL-12 (31).…”

“…Although apoptotic cells have certainly been demonstrated to suppress DC inflammatory cytokine production (11), the physiological contribution of CR3/iC3b interactions toward this effect remains in question. Furthermore, there are multiple conflicting reports on the ability of CR3/iC3b interactions to enhance the phagocytosis and internalization of apoptotic cells (10,(12)(13)(14). Because apoptosis is an asynchronous event, it is difficult to generate homogenous populations of apoptotic cells.…”

Expression and role of Fc- and complement-receptors on human dendritic cells

“…Preynat-Seauve et al investigated the possible cross talk between Fc␥RIII, the low affinity receptor for IgG, and CR3 [59]. They found that the interaction of these receptors enhances iC3b binding to monocyte CR3 but the cooperation between CD16 and CR3 is lost during differentiation of monocytes into DCs.…”

Costimulation of Dectin-1 and DC-SIGN Triggers the Arachidonic Acid Cascade in Human Monocyte-Derived Dendritic Cells

“…The C3bi moiety incorporated into IC binds to CR3 (Mac-1, CD11b/CD18, ␣ M ␤ 2 integrin) and drives the immune load from Fc␥R to CR3, thus promoting phagocytosis by monocytes in the absence of inflammatory response. Notably, productive binding of C3bi to leukocyte-expressed CR3 needs an interaction with Fc␥RIII to form a CR3/Fc␥RIII complex, the formation of which is impeded in DC (57). DC show a high expression of CD11c, i.e., the ␣-chain of CR4, another integrin with C3bi-binding properties.…”