β1-integrin mediates pressure-stimulated phagocytosis

BackgroundExtracellular pressure alterations in infection, inflammation, or positive pressure ventilation may influence macrophage phagocytosis. We hypothesized that pressure modulates β1-integrins to stimulate phagocytosis.MethodsWe assayed fibroblast phagocytosis of fluorescent latex beads at ambient or 20 mm Hg increased pressure, and macrophage integrin phosphorylation by Western blot.ResultsPressure did not alter phagocytosis in β1-integrin null GD25 fibroblasts, but stimulated phagocytosis in fibroblasts expressing wild-type β1-integrin. In phorbol myristate acetate-differentiated THP-1 macrophages, pressure stimulated β1-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.ConclusionsThe 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 β1-integrin T789 phosphorylation. Interventions that target β1-integrin threonine 789 phosphorylation may modulate phagocytic function.