Yan-Xiong Mao1, Jin-Fu Xu2, Eric J Seeley3, Xiao-Dan Tang1, Lu-Lu Xu1, Ying-Gang Zhu1, Yuan-Lin Song4, Jie-Ming Qu1,5. 1. Department of Pulmonary Medicine, Huadong Hospital and d, Fudan University, Shanghai, People's Republic of China. 2. Department of Pulmonary Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China. 3. Department of Pulmonary and Critical Care Medicine, University of California, San Francisco, USA. 4. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China. 5. Department of Pulmonary Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Abstract
RATIONALE: New strategies for treating Pseudomonas aeruginosa pulmonary infection are urgently needed. Adipose tissue-derived mesenchymal stem cells (ASCs) may have a potential therapeutic role in P. aeruginosa-induced pulmonary infection. METHODS: The therapeutic and mechanistic effects of ASCs on P. aeruginosa pulmonary infection were evaluated in a murine model of P. aeruginosa pneumonia. RESULTS: ASCs exhibited protective effects against P. aeruginosa pulmonary infection, evidenced by reduced bacterial burdens, inhibition of alveolar neutrophil accumulation, decreased levels of myeloperoxidase, macrophage inflammatory protein-2 and total proteins in broncho-alveolar lavage fluid (BALF), and attenuated severity of lung injury. ASCs had no effects on BALF and serum levels of keratinocyte growth factor or Ang-1. ASCs had no effects on the levels of insulin growth factor 1 (IGF-1) in BALF, but increased IGF-1 levels in serum. ASCs inhibited the overproduction of prostaglandin E2 (PGE2 ) by decreasing the expression of cyclooxygenase-2 (COX2) and enhancing the expression of 15-PGDH. In addition, the addition of exogenous PGE2 with ASCs abolished many of the protective effects of ASCs, and administrating PGE2 alone exacerbated lung infection. By inhibiting production of PGE2 , ASCs improved phagocytosis and the bactericidal properties of macrophages. Furthermore suppressing PGE2 signaling by COX2 inhibition or EP2 inhibition exhibited protective effects against pulmonary infection as well. CONCLUSIONS: In a murine model of P. aeruginosa pneumonia, ASCs exhibited protective effects by inhibiting production of PGE2 , which subsequently improved phagocytosis and the bactericidal properties of macrophages. ASCs may provide a new strategy for managing pulmonary infection caused by P. aeruginosa.
RATIONALE: New strategies for treating Pseudomonas aeruginosa pulmonary infection are urgently needed. Adipose tissue-derived mesenchymal stem cells (ASCs) may have a potential therapeutic role in P. aeruginosa-induced pulmonary infection. METHODS: The therapeutic and mechanistic effects of ASCs on P. aeruginosa pulmonary infection were evaluated in a murine model of P. aeruginosa pneumonia. RESULTS: ASCs exhibited protective effects against P. aeruginosa pulmonary infection, evidenced by reduced bacterial burdens, inhibition of alveolar neutrophil accumulation, decreased levels of myeloperoxidase, macrophage inflammatory protein-2 and total proteins in broncho-alveolar lavage fluid (BALF), and attenuated severity of lung injury. ASCs had no effects on BALF and serum levels of keratinocyte growth factor or Ang-1. ASCs had no effects on the levels of insulin growth factor 1 (IGF-1) in BALF, but increased IGF-1 levels in serum. ASCs inhibited the overproduction of prostaglandin E2 (PGE2 ) by decreasing the expression of cyclooxygenase-2 (COX2) and enhancing the expression of 15-PGDH. In addition, the addition of exogenous PGE2 with ASCs abolished many of the protective effects of ASCs, and administrating PGE2 alone exacerbated lung infection. By inhibiting production of PGE2 , ASCs improved phagocytosis and the bactericidal properties of macrophages. Furthermore suppressing PGE2 signaling by COX2 inhibition or EP2 inhibition exhibited protective effects against pulmonary infection as well. CONCLUSIONS: In a murine model of P. aeruginosa pneumonia, ASCs exhibited protective effects by inhibiting production of PGE2 , which subsequently improved phagocytosis and the bactericidal properties of macrophages. ASCs may provide a new strategy for managing pulmonary infection caused by P. aeruginosa.
Authors: Yunfei Xu; Haoduo Qiao; Shun Yang; Lin Zhou; Yao Zhao; Qing Xu; Shuying Miao; Dun Yuan; Jie Zhao; Ying Liu Journal: Front Neurol Date: 2022-05-26 Impact factor: 4.086