Research article

Macropinocytosis is decreased in diabetic mouse macrophages and is regulated by AMPK

Christopher B Guest^1,2 , Kenneth S Chakour² and Gregory G Freund^1,2

¹Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, USA

²Pathology, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, USA

author email corresponding author email

BMC Immunology 2008, 9:42doi:10.1186/1471-2172-9-42

Published:	30 July 2008

Abstract

Background

Macrophages (MΦs) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized by metabolic abnormalities and altered immune function. Here we examine the influence of diabetes on macropinocytosis in primary mouse macrophages and in an in vitro diabetes model.

Results

The data demonstrate that peritoneal MΦs from diabetic (db/db) mice had reduced macropinocytosis when compared to MΦs from non-diabetic (db/+) mice. Additionally, MΦs cultured in hyperglycemic conditions were less adept at macropinocytosis than those cultured in low glucose. Notably, AMP-activated protein kinase (AMPK) activity was decreased in MΦs cultured in hyperglycemic conditions. Activation of AMPK with leptin or 5-aminoimidazole-4-carboxamide-1-β-riboside (AICAR) increased macropinocytosis and inhibition of AMPK with compound C decreased macropinocytosis.

Conclusion

Taken together, these findings indicate that MΦs from diabetic mice have decreased macropinocytosis. This decrease appears dependent on reduced AMPK activity. These results demonstrate a previously unrealized role for AMPK in MΦs and suggest that increasing AMPK activity in diabetic MΦs could improve innate immunity and decrease susceptibility to infection.