Taurine chloramine potentiates phagocytic activity of peritoneal macrophages through up-regulation of dectin-1 mediated by heme oxygenase-1-derived carbon monoxide.

Resolution of inflammation that occurs after microbial infection or tissue damage is an important physiologic process in maintaining or restoring host homeostasis. Taurine chloramine (TauCl) is formed by a reaction between taurine and hypochlorite in leukocytes, and it is especially abundant in activated neutrophils that encounter an oxidative burst. As neutrophils undergo apoptosis, TauCl is released to the extracellular matrix at the inflamed sites, thereby affecting coexisting macrophages in the inflammatory microenvironment. In this study, we investigated the role of TauCl in phagocytosis by macrophages during resolution of fungal infection-induced inflammation. We found that exogenous TauCl substantially increased the phagocytic efficiency of macrophages through up-regulation of dectin-1, a receptor for fungal beta-1,3-glucans, which is present on the membrane of macrophages. Our previous studies demonstrated the induction of heme oxygenase-1 (HO-1) expression in murine peritoneal macrophages treated with TauCl. In the present study, knocking out HO-1 or pharmacologic inhibition of HO-1 with zinc protoporphyrin IX attenuated the TauCl-induced expression of dectin-1 and subsequent phagocytosis. Furthermore, carbon monoxide (CO), a by-product of the HO-1-catalyzed reaction, induced expression of dectin-1 and potentiated phagocytic capability of the macrophages, which appeared to be mediated through up-regulation of peroxisome proliferator-activated receptor . Taken together, induction of HO-1 expression and subsequent CO production by TauCl are essential for phagocytosis of fungi by macrophages. Our results suggest that TauCl has important roles in host defense against fungal infection and has therapeutic potential in the management of inflammatory diseases.