title: NEGATIVE REGULATORY EFFECTS OF PHOSPHATIDYLINOSITOL3-KINASE PATHWAY ON PHAGOCYTOSIS AND MACROPINOCYTOSIS IN BOVINE MONOCYTES.
abstract: Recent studies have shown that monocytes and macrophages not only present antigens to effector T cells and stimulate and shape T cell-mediated immune responses, but they also prime naïve T cells, thus initiating adaptive immune responses. Phosphatidylinositol 3-kinase functions at an early phase of toll-like receptor signaling pathways, modulates the magnitude of the primary immune responses, and is involved in the reorganization of the actin cytoskeleton during macropinocytic and phagocytic antigen uptakes, important early steps in triggering adaptive immune responses. We assessed by flow cytometry the endocytic capacities of bovine monocytes by using endocytic tracers andSalmonellatransformed with a green fluorescence plasmid GFP to evaluate macropinocytosis, mannose receptor-mediated endocytosis, and phagocytosis in bovine professional antigen presenting cells, respectively. Our data reveal that wortmannin, an inhibitor of phosphatidylinositol 3-kinase signaling pathway, significantly increased macropinocytosis and phagocytosis but did not affect the mannose receptor-mediated antigen uptake in bovine monocytes. Protein expression data support these findings by showing decreased levels of phosphoinositide 3-kinase in the presence of wortmannin during macropinocytosis. We expanded further the key role of phosphatidylinositol 3-kinase as an endogenous suppressor of primary immune responses, suggesting a novel mechanism of phosphatidylinositol 3-kinase antigen uptake modulation that may provide a unique therapeutic target for controlling excessive inflammation.
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, 240 Wise Center Drive, Mississippi State, MS 39762, USA.
authors.forename: Mais G
authors.initials: MG
authors.lastname: Ammari
authors.affiliation: School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Autumn N
authors.initials: AN
authors.lastname: Harris
authors.affiliation: Department of Small Animal Internal Medicine, University of Florida, Gainesville, FL 32611, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Stokes
authors.affiliation: Department of Pathobiology and Population Medicine, Mississippi State, MS 39762, USA.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Bailey
authors.forename: Lesya M
authors.initials: LM
authors.lastname: Pinchuk
keywords: Antigen Uptake; Macropinocytosis; Monocytes; Phagocytosis; Phosphatidylinositol 3-Kinase Pathway; Receptor-Mediated Endocytosis; Wortmannin