beta(1)-integrin mediates pressure-stimulated phagocytosis.
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.
Bhalla
Sean
S
Department of Surgery, John D Dingell VA Medical Center, Detroit, MI, USA.
Shiratsuchi
Hiroe
H
Craig
David H
DH
Basson
Marc D
MD
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D019012:Integrin beta1 / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D010587:Phagocytosis / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D011312:Pressure
D019012:Integrin beta1