BACKGROUND: Extracellular pressure alterations in infection, inflammation, or positive pressure ventilation may influence macrophage phagocytosis. We hypothesized that pressure modulates beta1-integrins to stimulate phagocytosis. METHODS: We assayed fibroblast phagocytosis of fluorescent latex beads at ambient or 20 mm Hg increased pressure, and macrophage integrin phosphorylation by Western blot. RESULTS: Pressure did not alter phagocytosis in beta(1)-integrin null GD25 fibroblasts, but stimulated phagocytosis in fibroblasts expressing wild-type beta(1)-integrin. In phorbol myristate acetate-differentiated THP-1 macrophages, pressure stimulated beta(1)-integrin T788/789 phosphorylation, but not S785 phosphorylation. Furthermore, pressure stimulated phagocytosis in cells expressing an inactivating S785A point mutation or a T788D substitution to mimic a constitutively phosphorylated threonine, but not in cells expressing an inactivating TT788/9AA mutation. CONCLUSIONS: The effects of pressure on phagocytosis are not limited to macrophages but generalize to other phagocytic cells. These results suggest that pressure stimulates phagocytosis via increasing beta(1)-integrin T789 phosphorylation. Interventions that target beta(1)-integrin threonine 789 phosphorylation may modulate phagocytic function.
BACKGROUND: Extracellular pressure alterations in infection, inflammation, or positive pressure ventilation may influence macrophage phagocytosis. We hypothesized that pressure modulates beta1-integrins to stimulate phagocytosis. METHODS: We assayed fibroblast phagocytosis of fluorescent latex beads at ambient or 20 mm Hg increased pressure, and macrophage integrin phosphorylation by Western blot. RESULTS: Pressure did not alter phagocytosis in beta(1)-integrin null GD25 fibroblasts, but stimulated phagocytosis in fibroblasts expressing wild-type beta(1)-integrin. In phorbol myristate acetate-differentiated THP-1 macrophages, pressure stimulated beta(1)-integrin T788/789 phosphorylation, but not S785 phosphorylation. Furthermore, pressure stimulated phagocytosis in cells expressing an inactivating S785A point mutation or a T788D substitution to mimic a constitutively phosphorylated threonine, but not in cells expressing an inactivating TT788/9AA mutation. CONCLUSIONS: The effects of pressure on phagocytosis are not limited to macrophages but generalize to other phagocytic cells. These results suggest that pressure stimulates phagocytosis via increasing beta(1)-integrin T789 phosphorylation. Interventions that target beta(1)-integrinthreonine 789 phosphorylation may modulate phagocytic function.
Authors: Anca Sindrilaru; Thorsten Peters; Jürgen Schymeinsky; Tsvetelina Oreshkova; Honglin Wang; Anne Gompf; Francesca Mannella; Meinhard Wlaschek; Cord Sunderkötter; Karl Lenhard Rudolph; Barbara Walzog; Xosé R Bustelo; Klaus D Fischer; Karin Scharffetter-Kochanek Journal: Blood Date: 2009-01-15 Impact factor: 22.113
Authors: Guangxiang Yu; Michael Dymond; Lisi Yuan; Lakshmi S Chaturvedi; Hiroe Shiratsuchi; Srinivasan Durairaj; H Michael Marsh; Marc D Basson Journal: Surgery Date: 2011-06-15 Impact factor: 3.982