In this Issue 2016; 196:3215-3216

ARRUVITO LOURDES; JULIETA PANDOLFI; BILLORDO LUIS ARIEL; BAZ PLÁCIDA

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2016 vol. 2016 p. 3215 - 3216

0022-1767

Antibody targeting of theadhesion molecule CD44has been used in animalmodels for the treatment of inflammatoryand autoimmune diseases,some of which may involve dysregulationof phagocytosis. Phagocytosisis induced by a variety of surfacereceptors, including Fcg receptors(FcgRs), complement receptors,and nonopsonic receptors such as dectin-1. In this issue,Amash et al. (p. 3331) investigate the influence of the wellstudiedanti-CD44 mAb IM7 on macrophage phagocytosis.IM7 pretreatment of RAW264.7 (RAW) macrophages orprimary peritoneal macrophages prevented FcgR-mediatedphagocytosis of IgG-opsonized SRBCs in a dose-dependentmanner; phagocytic inhibition was lower in primary macrophagesthan in RAW cells, potentially due to population heterogeneity.Other anti-CD44 mAbs investigated were unableto inhibit FcgR-mediated phagocytosis of RAW macrophagesat any dose tested. IM7 could inhibit macrophage bindingto target cells and was also able to prevent phagocytosis whenadded after macrophage-target cell binding, suggesting thatIM7 interferes with phagocytosis at multiple stages. Althoughthe F(ab9)2 form of IM7 was capable of binding RAW cells, itcould not inhibit phagocytosis, implicating the Fc portion inthis process. IM7 also inhibited complement receptor 3?mediatedphagocytosis of C3bi-opsonized SRBCs, but not dectin-1-mediated phagocytosis of zymosan particles. Collectively,these results show that the anti-CD44 mAb IM7 enacts some of its potent anti-inflammatory effects by inhibiting opsonic receptor-mediated phagocytosis.