title: Differential effects of gram-positive and gram-negative bacterial products on morphine induced inhibition of phagocytosis.
abstract: Opioid drug abusers have a greater susceptibility to gram positive (Gram (+)) bacterial infections. However, the mechanism underlying opioid modulation of Gram (+) versus Gram (-) bacterial clearance has not been investigated. In this study, we show that opioid treatment resulted in reduced phagocytosis of Gram (+), when compared to Gram (-) bacteria. We further established that LPS priming of chronic morphine treated macrophages leads to potentiated phagocytosis and killing of both Gram (+) and Gram (-) bacteria in a P-38 MAP kinase dependent signaling pathway. In contrast, LTA priming lead to inhibition of both phagocytosis and bacterial killing. This study demonstrates for the first time the differential effects of TLR4 and TLR2 agonists on morphine induced inhibition of phagocytosis. Our results suggest that the incidence and severity of secondary infections with Gram (+) bacteria would be higher in opioid abusers.
authors.forename: Jana
authors.initials: J
authors.lastname: Ninkovic
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Ninkovic
authors.initials: N
authors.lastname: Jana
authors.forename: Vidhu
authors.initials: V
authors.lastname: Anand
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Anand
authors.initials: A
authors.lastname: Vidhu
authors.forename: Raini
authors.initials: R
authors.lastname: Dutta
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Dutta
authors.initials: D
authors.lastname: Raini
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Anuj
authors.initials: A
authors.lastname: Saluja
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Meng
authors.forename: Lisa
authors.initials: L
authors.lastname: Koodie
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Koodie
authors.initials: K
authors.lastname: Lisa
authors.forename: Santanu
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Banerjee
authors.initials: B
authors.lastname: Santanu
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455.|Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Sabita
authors.initials: S
authors.lastname: Roy
authors.forename: Roy
authors.initials: R
authors.lastname: Sabita
mesh_terms: D000818:Animals; D015870:Gene Expression; D006090:Gram-Negative Bacteria / Q000276:immunology / Q000378:metabolism*; D006094:Gram-Positive Bacteria / Q000276:immunology / Q000378:metabolism*; D056747:Immunomodulation; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D050296:Microbial Viability / Q000187:drug effects / Q000276:immunology; D008954:Models, Biological; D009020:Morphine / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D013682:Teichoic Acids / Q000276:immunology / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D008024:Ligands; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C009900:lipoteichoic acid; D009020:Morphine