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Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
Medical School
Department of Surgery

PI: Sabita Roy

Chronic Morphine Modulates Fc-gamma Receptor Mediated Phagocytosis via cAMP Mechanism

Morphine has been known to inhibit innate immunity. Several studies show that morphine inhibits phagocytosis, but the mechanistic of this inhibition remains to be explained. The group’s results show that chronic morphine treatment, in vitro and in vivo, modulates Fc-gamma receptor-mediated phagocytosis in murine macrophages. Using fluorescence microscopy and fluorometry, following chronic morphine treatment, decreased internalization of opsonized FITC tagged Escherichia coli bacterial particles as well as opsonized live GFP tagged E. coli is found. Microscopic analysis shows that chronic morphine leads to decrease in formation of pseudopodia and phagosomal cups, indicating morphine’s modulation of actin polymerization via small GTP-ases such as Cdc42, Rac and Rho. Forskolin-induced elevation of cAMP levels in macrophage cell line led to suppression of Fc-gamma receptor-mediated phagocytosis in morphine and vehicle treated cells. In addition, H89 induced inhibition of PKA resulted in increased phagocytosis of opsonized bacteria. Together these data indicate that chronic morphine inhibits phagocytosis via a cAMP and PKA dependant pathway, ultimately affecting actin polymerization. The researchers’ ongoing studies will further elucidate the mechanism of morphine-induced decrease of bacterial internalization and its role in modulation of key initiators of phagocytosis such as Cdc42, Rac and Rho kinase.

Group Member

Jana Ninkovic, Graduate Student