{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:01:02Z","timestamp":1779195662217,"version":"3.51.4"},"reference-count":71,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Program on Key Research Project of China","award":["SQ2022YFD1800030"],"award-info":[{"award-number":["SQ2022YFD1800030"]}]},{"name":"National Program on Key Research Project of China","award":["Grant No. 31872455"],"award-info":[{"award-number":["Grant No. 31872455"]}]},{"name":"National Natural Sciences Foundation of China","award":["SQ2022YFD1800030"],"award-info":[{"award-number":["SQ2022YFD1800030"]}]},{"name":"National Natural Sciences Foundation of China","award":["Grant No. 31872455"],"award-info":[{"award-number":["Grant No. 31872455"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alveolar macrophage (AM) proliferation and self-renewal play an important role in the lung tissue microenvironment. However, the impact of immune cells, especially the neutrophils, on AM homeostasis or function is not well characterized. In this study, we induced in vivo migration of neutrophils into bronchoalveolar lavage (BAL) fluid and lung using CXCL1, and then co-cultured these with AMs in vitro. Neutrophils in the BAL (BAL\u2212neutrophils), rather than neutrophils of bone marrow (BM-neutrophils), were found to inhibit AM proliferation. Analysis of publicly available data showed high heterogeneity of lung neutrophils with distinct molecular signatures of BM\u2212 and blood\u2212neutrophils. Unexpectedly, BAL\u2212neutrophils from influenza virus PR8-infected mice (PR8\u2212neutrophils) did not inhibit the proliferation of AMs. Bulk RNA sequencing further revealed that co-culture of AMs with PR8\u2212neutrophils induced IFN-\u03b1 and -\u03b3 responses and inflammatory response, and AMs co-cultured with BAL\u2212neutrophils showed higher expression of metabolism- and ROS-associated genes; in addition, BAL\u2212neutrophils from PR8-infected mice modulated AM polarization and phagocytosis. BAL\u2212neutrophil-mediated suppression of AM proliferation was abrogated by a combination of inhibitors of different neutrophil death pathways. Collectively, our findings suggest that multiple cell death pathways of neutrophils regulate the proliferation of AMs. Targeting neutrophil death may represent a potential therapeutic strategy for improving AM homeostasis during respiratory diseases.<\/jats:p>","DOI":"10.3390\/cells11223633","type":"journal-article","created":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T03:26:04Z","timestamp":1668655564000},"page":"3633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multiple Death Pathways of Neutrophils Regulate Alveolar Macrophage Proliferation"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3381-2489","authenticated-orcid":false,"given":"Xiaochen","family":"Gao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijia","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Su","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanru","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen F.","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China"},{"name":"Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People\u2019s Republic of China, Wuhan 430070, China"},{"name":"International Research Center for Animal Disease, Ministry of Science and Technology of the People\u2019s Republic of China, Wuhan 430070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","first-page":"81","article-title":"Alveolar Macrophages: Plasticity in a Tissue-Specific Context. 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