Exosomal secreted SCIMP regulates communication between macrophages and neutrophils in pneumonia

Xiaolei Pei (), Li Liu, Jieru Wang, Changyuan Guo, Qingqing Li, Jia Li, Qian Ren, Runzhi Ma, Yi Zheng, Yan Zhang, Li Liu, Danfeng Zheng, Pingzhang Wang, Ping Jiang, Xiaoming Feng, Erlie Jiang, Ying Wang () and Sizhou Feng ()
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Xiaolei Pei: Chinese Academy of Medical Sciences & Peking Union Medical College
Li Liu: Chinese Academy of Medical Sciences & Peking Union Medical College
Jieru Wang: Chinese Academy of Medical Sciences & Peking Union Medical College
Changyuan Guo: Peking University
Qingqing Li: Peking University
Jia Li: Chinese Academy of Medical Sciences & Peking Union Medical College
Qian Ren: Chinese Academy of Medical Sciences & Peking Union Medical College
Runzhi Ma: Chinese Academy of Medical Sciences & Peking Union Medical College
Yi Zheng: Peking University
Yan Zhang: Peking University
Li Liu: Tianjin Medical University
Danfeng Zheng: Peking University
Pingzhang Wang: Peking University
Ping Jiang: Tianjin Medical University
Xiaoming Feng: Chinese Academy of Medical Sciences & Peking Union Medical College
Erlie Jiang: Chinese Academy of Medical Sciences & Peking Union Medical College
Ying Wang: Peking University
Sizhou Feng: Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract In pneumonia, the deficient or delayed pathogen clearance can lead to pathogen proliferation and subsequent overactive immune responses, inducing acute lung injury (ALI). While screening human genome coding genes using our peripheral blood cell chemotactic platform, we unexpectedly find SLP adaptor and CSK interacting membrane protein (SCIMP), a protein with neutrophil chemotactic activity secreted during ALI. However, the specific role of SCIMP in ALI remains unclear. In this study, we investigate the secretion of SCIMP in exosomes (SCIMPexo) by macrophages after bacterial stimulation, both in vitro and in vivo. We observe a significant increase in the levels of SCIMPexo in bronchoalveolar lavage fluid and serum of pneumonia patients. We also find that bronchial perfusion with SCIMPexo or SCIMP N-terminal peptides increases the survival rate of the ALI model. This occurs due to the chemoattraction and activation of peripheral neutrophils dependent on formyl peptide receptor 1/2 (FPR1/2). Conversely, exosome suppressors and FPR1/2 antagonists decrease the survival rate in the lethal ALI model. Scimp-deficient and Fpr1/2-deficient mice also have lower survival rates and shorter survival times than wild-type mice. However, bronchial perfusion of SCIMP rescues Scimp-deficient mice but not Fpr1/2-deficient mice. Collectively, our findings suggest that the macrophage-SCIMP-FPRs-neutrophil axis plays a vital role in the innate immune process underlying ALI.

Date: 2024
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DOI: 10.1038/s41467-024-44714-4

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