title: Phagocytic activity of LPS tolerant macrophages.
abstract: Endotoxin tolerance is defined as a reduced capacity of the host to respond to LPS activation following a first exposure to this stimulus. It affects all leukocytes and regarding macrophages, most studies focus on the reduced ability of these cells to secrete pro-inflammatory cytokines. Therefore, we evaluated other macrophages functions (fungicidal capacity, reactive oxygen species production and antigen presentation) in cells from tolerant mice. We have performed a tolerance model in our laboratory that does not stimulate directly the place from where the cells will be removed (peritoneal cavity). Mouse received subcutaneous injections of LPS in the scruff for 5 days and we analyze the capacity of peritoneal macrophages to phagocyte using three different receptors: Fc, C3b and mannose receptors. We found a reduction in the phagocytosis of erythrocytes and Candida albicans related to the Fc and mannose receptors. These differences can be due to a macrophage reprogramming, as demonstrated by altered expression of cytokines and chemokines. Despite this reduction in phagocytosis capacity, macrophages from tolerant animals exhibited enhanced hydrogen peroxide production and expression of antigen presentation molecules, suggesting that their ability to combat an infection is improved. In summary, our data indicates that LPS tolerance drives macrophages from a predominant release of proinflammatory mediators that amplify inflammation and host damage toward a better killing and antigen presentation state.
authors.affiliation: Emergency Medicine Department, Medical School, University of São Paulo, São Paulo, Brazil. Electronic address: thaismlima@gmail.com.
authors.forename: Thais Martins
authors.initials: TM
authors.lastname: de Lima
authors.affiliation: Laboratory of Pathophysiology, Butantan Institute, São Paulo, SP, Brazil.
authors.forename: Sandra Coccuzzo
authors.initials: SC
authors.lastname: Sampaio
authors.affiliation: Emergency Medicine Department, Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Petroni
authors.affiliation: Laboratory of Pathophysiology, Butantan Institute, São Paulo, SP, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Brigatte
authors.affiliation: Emergency Medicine Department, Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Irineu Tadeu
authors.initials: IT
authors.lastname: Velasco
authors.affiliation: Emergency Medicine Department, Medical School, University of São Paulo, São Paulo, Brazil.
authors.forename: Francisco Garcia
authors.initials: FG
authors.lastname: Soriano
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology; D017463:Receptors, Complement 3b / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology
chemical_list: D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D006861:Hydrogen Peroxide
keywords: Antimicrobial activity; Endotoxin tolerance; Macrophages; Phagocytosis