Akt1 is critical for acute inflammation and histamine-mediated vascular leakage

• DOI: 10.1073/pnas.0904073106
• Publication Date: 2009-07-22T01:07:45Z
• Authors: Annarita Di Lorenzo; Carlos Fernández-...; Giuseppe Cirino; William C. Sessa
• Keywords: Vascular permeability; Leukocyte extravasation; AKT2; Extravasation

Akt1 is implicated in cell metabolism, survival migration, and gene expression; however, little known about the role of specific Akt isoforms during inflammation vivo. Thus, we directly explored roles Akt2 acute models by using mice deficient either or Akt2. −/− showed a markedly reduced edema versus WT controls, was associated with dramatic decrease neutrophil monocyte infiltration. The loss did not affect leukocyte functions vitro, bone marrow transplant experiments suggest that host regulates emigration into inflamed tissues. Moreover, carrageenan-induced direct propermeability actions bradykinin histamine were dramatically mice. These findings are supported vitro showing deficiency blockade nitric oxide synthase reduces histamine-stimulated changes transendothelial electrical resistance microvascular endothelial cells. Collectively, these results necessary for exerts its primarily via regulation vascular permeability, leading to extravasation.