β1-integrin mediates pressure-stimulated phagocytosis

Bhalla, Sean; Shiratsuchi, Hiroe; Craig, David H.; Basson, Marc D.

doi:10.1016/j.amjsurg.2009.07.006

« Previous Next »The American Journal of Surgery
Volume 198, Issue 5 , Pages 611-616, November 2009

β₁-integrin mediates pressure-stimulated phagocytosis

Sean Bhalla
- Department of Surgery, John D. Dingell VA Medical Center, Detroit, MI, USA
- Department of Surgery, Wayne State University, Detroit, MI, USA
Hiroe Shiratsuchi, Ph.D.
- Department of Surgery, John D. Dingell VA Medical Center, Detroit, MI, USA
- Department of Surgery, Wayne State University, Detroit, MI, USA
David H. Craig, Ph.D.
- Department of Surgery, John D. Dingell VA Medical Center, Detroit, MI, USA
- Department of Surgery, Michigan State University, 1200 E. Michigan Ave., Suite 655, Lansing, MI 48912, USA
Marc D. Basson, M.D., Ph.D.
- Department of Surgery, John D. Dingell VA Medical Center, Detroit, MI, USA
- Department of Surgery, Michigan State University, 1200 E. Michigan Ave., Suite 655, Lansing, MI 48912, USA
- Corresponding author. Tel.: +1-517-267-2477; fax: +1-517-267-2488

Received 30 April 2009; received in revised form 2 July 2009

Abstract

Background

Extracellular pressure alterations in infection, inflammation, or positive pressure ventilation may influence macrophage phagocytosis. We hypothesized that pressure modulates β1-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 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.

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 β₁-integrin T789 phosphorylation. Interventions that target β₁-integrin threonine 789 phosphorylation may modulate phagocytic function.

Keywords: Inflammation, Integrin, Macrophage, Mechanotransduction, Phosphorylation, Pressure, Signaling