The function of human NK cells is enhanced by β‐glucan, a ligand of CR3 (CD11b/CD18)

Abstract

Cells responsible for the natural killer (NK) effect in the human blood can be collected in the low-density lymphocyte subset and the majority of them express CR3. In addition to the iC3b binding site the CR3 molecules possess an epitope which binds beta-glucan. Ligands of this site can deliver activation signals to CR3-carrying monocytes and neutrophils. We found that the function of NK cells was also potentiated by preincubation with beta-glucan. The treatment increased the proportion of target-binding lymphocytes and of the damaged target cells in the conjugates. The monoclonal antibody OKM-1, directed to the beta-glucan-binding site of CR3, abrogated this effect. Another CR3-reactive monoclonal antibody, M522, known to activate monocytes and neutrophils, enhanced the NK function.

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“…M522 is the only MoAb to CR3 that has been reported to stimulate a neutrophil respiratory burst [30], Taken together, these results suggest that M522 binds at or near to the same sile in CR3 as does //-glucan. Our own recent experiments have confirmed the linding of Di Renzo et al [29] and in addition have shown that the /J-glucanenhanced killing of K562 cells is blocked by staurosporine, genistein. or herbimycin A, These kinase inhibitors blocked only the enhancement of cytotoxicity stimulated by /i-glucan, and not the basal levels of CR3-independent cytotoxicity.…”

“…In addition. NK cells were shown to be similarly activated by F(ab'); fragments ofthe anti-CR3 MoAb M522 [29]. M522 is the only MoAb to CR3 that has been reported to stimulate a neutrophil respiratory burst [30], Taken together, these results suggest that M522 binds at or near to the same sile in CR3 as does //-glucan.…”

The human β‐glucan receptor is widely expressed and functionally equivalent to murine Dectin‐1 on primary cells

“…It has been shown that b-glucans modulate NK cell function through a receptor distinct from CR3 [21,33]. However, we did not detect the bGR on these cells (CD56 + CD16 + ) (Fig.…”

“…The activity of bGR has been described on a variety of human leukocytes including monocytes [17], macrophages [18], eosinophils [19], neutrophils [20] and NK cells [21], and we had previously detected bGR mRNA in some of these cell populations [10]. To demonstrate the presence of this receptor on these cells, we examined surface expression of bGR on human PBL by flow cytometry, using GE2 to detect both major functional bGR isoforms.…”

CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multiple ligand specificities and functions

“…Not only did anti-CR3 fail to inhibit NK cell killing of K562 cells [27], but aiso NKcell attachment to target cells coated with fixed iC3b did not stimulate cytotoxicity [4.28]. Recognizing the potential of jiglucan to activate neutrophil CR3, Di Renzo a ai [29] showed that soluble /f-glucan would greatly enhance NK cell-mediated cytotoxicity of K562 cells, and that this enhanced cytotoxicity was blocked by the anti-CR3 MoAb OKMl. In addition.…”