Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection.

This study examined the effects of the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count after pulmonary infection. Sprague‒Dawley rats were subjected to tracheal injection of lipopolysaccharide (LPS) to establish animal models of pulmonary infection. By inhibiting the PI3K/AKT pathway or inhibiting/inducing mitochondrial autophagy in macrophages, the severity of the pulmonary infection and the leukocyte count were altered. The PI3K/AKT inhibition group did not show a significant difference in leukocyte counts compared with the infection model group. Mitochondrial autophagy induction alleviated the pulmonary inflammatory response. The infection model group had significantly higher levels of LC3B, Beclin1, and p-mTOR than the control group. The AKT2 inhibitor group exhibited significantly increased levels of LC3B and Beclin1 compared with the control group ( < 0.05), and the Beclin1 level was significantly higher than that in the infection model group ( < 0.05). Compared with the infection model group, the mitochondrial autophagy inhibitor group exhibited significantly decreased levels of p-AKT2 and p-mTOR, whereas the levels of these proteins were significantly increased in the mitochondrial autophagy inducer group ( < 0.05). PI3K/AKT inhibition promoted mitochondrial autophagy in macrophages. Mitochondrial autophagy induction activated the downstream gene of the PI3K/AKT pathway, alleviated pulmonary inflammatory reactions, and decreased leukocyte counts.