{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:43:43Z","timestamp":1791607423932,"version":"4.3.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:00:00Z","timestamp":1341100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although great progress has been made in delineating lung dendritic cell and lymphocyte subpopulations, similar advances in lung macrophages (M\u03a6s) have been hampered by their intrinsic autofluorescence, cell plasticity, and the complexities of monocyte\u2013M\u03a6 compartmentalization. Using spectral scanning, we define alveolar M\u03a6 autofluorescence characteristics, which has allowed us to develop an alternative flow cytometry method. Using this methodology, we show that mouse lung M\u03a6s form distinct subpopulations during acute inflammation after challenge with LPS or influenza virus, and in chronic inflammatory lung disease consequent to SHIP-1 deletion. These subpopulations are distinguished by differential Mac-1 and CD11c integrin expression rather than classical M1 or M2 markers, and display differential gene signatures ex vivo. Whereas the resolution of acute inflammation is characterized by restoration to a homogenous population of CD11chighMac-1neg\/low M\u03a6s reflective of lung homeostasis, chronic inflammatory lung disease associated with SHIP-1 deficiency is accompanied by an additional subpopulation of CD11chighMac-1pos M\u03a6s that tracks with lung disease in susceptible genetic background SHIP-1\u2212\/\u2212 animals and disease induction in chimeric mice. These findings may help better understand the roles of M\u03a6 subpopulations in lung homeostasis and disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1200660","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T05:53:23Z","timestamp":1339480403000},"page":"946-955","source":"Crossref","is-referenced-by-count":113,"title":["Distinct Macrophage Subpopulations Characterize Acute Infection and Chronic Inflammatory Lung Disease"],"prefix":"10.1093","volume":"189","author":[{"given":"Mubing","family":"Duan","sequence":"first","affiliation":[{"name":"Ludwig Institute for Cancer Research , Melbourne, Victoria 3050,","place":["Australia"]},{"name":"Department of Surgery, University of Melbourne , Melbourne, Victoria 3010,","place":["Australia"]},{"name":"Leukocyte Signaling Laboratory, Department of Immunology, Monash University, Central Clinical School, Alfred Medical Research and Education Precinct , Melbourne, Victoria 3004,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waichu C","family":"Li","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research , Melbourne, Victoria 3050,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Vlahos","sequence":"additional","affiliation":[{"name":"Lung Disease Research Group, Department of Pharmacology, University of Melbourne , Melbourne, Victoria 3010,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mhairi J","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research , Melbourne, Victoria 3050,","place":["Australia"]},{"name":"Leukocyte Signaling Laboratory, Department of Immunology, Monash University, Central Clinical School, Alfred Medical Research and Education Precinct , Melbourne, Victoria 3004,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary P","family":"Anderson","sequence":"additional","affiliation":[{"name":"Lung Disease Research Group, Department of Pharmacology, University of Melbourne , Melbourne, Victoria 3010,","place":["Australia"]},{"name":"Department of Medicine, Royal Melbourne Hospital, University of Melbourne , Melbourne, Victoria 3010,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret L","family":"Hibbs","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research , Melbourne, Victoria 3050,","place":["Australia"]},{"name":"Leukocyte Signaling Laboratory, Department of Immunology, Monash University, Central Clinical School, Alfred Medical Research and Education Precinct , Melbourne, Victoria 3004,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,7,15]]},"reference":[{"key":"2025032409164329100_r1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nri3073","article-title":"Protective and pathogenic functions of macrophage subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"2025032409164329100_r2","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/ni.1937","article-title":"Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm","volume":"11","author":"Biswas","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025032409164329100_r3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages","volume":"3","author":"Gordon","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2025032409164329100_r4","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1146\/annurev.physiol.64.090601.113847","article-title":"Gm-CSF regulates pulmonary surfactant homeostasis and alveolar macrophage-mediated innate host defense","volume":"64","author":"Trapnell","year":"2002","journal-title":"Annu. Rev. Physiol."},{"key":"2025032409164329100_r5","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1016\/S0140-6736(02)11772-7","article-title":"Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?","volume":"360","author":"Cheung","year":"2002","journal-title":"Lancet"},{"key":"2025032409164329100_r6","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1084\/jem.20080201","article-title":"Lung epithelial apoptosis in influenza virus pneumonia: the role of macrophage-expressed TNF-related apoptosis-inducing ligand","volume":"205","author":"Herold","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025032409164329100_r7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nature01413","article-title":"Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema","volume":"422","author":"Morris","year":"2003","journal-title":"Nature"},{"key":"2025032409164329100_r8","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.immuni.2005.09.003","article-title":"SHIP represses the generation of alternatively activated macrophages","volume":"23","author":"Rauh","year":"2005","journal-title":"Immunity"},{"key":"2025032409164329100_r9","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S1074-7613(01)00218-7","article-title":"GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1","volume":"15","author":"Shibata","year":"2001","journal-title":"Immunity"},{"key":"2025032409164329100_r10","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1084\/jem.170.2.499","article-title":"Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice","volume":"170","author":"Thepen","year":"1989","journal-title":"J. Exp. Med."},{"key":"2025032409164329100_r11","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1165\/rcmb.2005-0241OC","article-title":"Resident alveolar macrophages are replaced by recruited monocytes in response to endotoxin-induced lung inflammation","volume":"35","author":"Maus","year":"2006","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2025032409164329100_r12","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1164\/ajrccm.165.1.2106148","article-title":"Molecular pathways of monocyte emigration into the alveolar air space of intact mice","volume":"165","author":"Maus","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025032409164329100_r13","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(03)00174-2","article-title":"Blood monocytes consist of two principal subsets with distinct migratory properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"2025032409164329100_r14","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.4049\/jimmunol.180.4.2562","article-title":"CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality","volume":"180","author":"Lin","year":"2008","journal-title":"J. Immunol."},{"key":"2025032409164329100_r15","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.4049\/jimmunol.0804096","article-title":"Important role for CC chemokine ligand 2-dependent lung mononuclear phagocyte recruitment to inhibit sepsis in mice infected with Streptococcus pneumoniae","volume":"182","author":"Winter","year":"2009","journal-title":"J. Immunol."},{"key":"2025032409164329100_r16","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1164\/ajrccm.158.4.9802078","article-title":"Severity of airflow limitation is associated with severity of airway inflammation in smokers","volume":"158","author":"Di Stefano","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025032409164329100_r17","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1182\/blood.V98.9.2845","article-title":"Alveolar macrophage deficiency in osteopetrotic mice deficient in macrophage colony-stimulating factor is spontaneously corrected with age and associated with matrix metalloproteinase expression and emphysema","volume":"98","author":"Shibata","year":"2001","journal-title":"Blood"},{"key":"2025032409164329100_r18","first-page":"924","article-title":"Regulation of myeloproliferation and M2 macrophage programming in mice by Lyn\/Hck, SHIP, and Stat5","volume":"118","author":"Xiao","year":"2008","journal-title":"J. Clin. Invest."},{"key":"2025032409164329100_r19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.etp.2006.02.009","article-title":"Specific aspects of flow cytometric analysis of cells from the lung","volume":"57","author":"Garn","year":"2006","journal-title":"Exp. Toxicol. Pathol."},{"key":"2025032409164329100_r20","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1101\/gad.13.7.786","article-title":"SHIP is a negative regulator of growth factor receptor-mediated PKB\/Akt activation and myeloid cell survival","volume":"13","author":"Liu","year":"1999","journal-title":"Genes Dev."},{"key":"2025032409164329100_r21","doi-asserted-by":"crossref","first-page":"7164","DOI":"10.4049\/jimmunol.1004185","article-title":"Genetic segregation of inflammatory lung disease and autoimmune disease severity in SHIP-1\u2212\/\u2212 mice","volume":"186","author":"Maxwell","year":"2011","journal-title":"J. Immunol."},{"key":"2025032409164329100_r22","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1164\/rccm.200912-1794OC","article-title":"Neutralizing granulocyte\/macrophage colony-stimulating factor inhibits cigarette smoke-induced lung inflammation","volume":"182","author":"Vlahos","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025032409164329100_r23","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1164\/ajrccm\/138.5.1124","article-title":"Use of allophycocyanin allows quantitative description by flow cytometry of alveolar macrophage surface antigens present in low numbers of cells","volume":"138","author":"Fuchs","year":"1988","journal-title":"Am. Rev. Respir. Dis."},{"key":"2025032409164329100_r24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/jemt.20191","article-title":"Fluorescent human lung macrophages analyzed by spectral confocal laser scanning microscopy and multispectral cytometry","volume":"67","author":"Pauly","year":"2005","journal-title":"Microsc. Res. Tech."},{"key":"2025032409164329100_r25","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nri1375","article-title":"Adhesion mechanisms regulating the migration of monocytes","volume":"4","author":"Imhof","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"2025032409164329100_r26","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.immuni.2004.07.010","article-title":"LPS-induced upregulation of SHIP is essential for endotoxin tolerance","volume":"21","author":"Sly","year":"2004","journal-title":"Immunity"},{"issue":"6","key":"2025032409164329100_r27","doi-asserted-by":"crossref","first-page":"301S","DOI":"10.1378\/chest.122.6_suppl.301S","article-title":"Animal models of cigarette smoke-induced COPD","volume":"122","author":"Wright","year":"2002","journal-title":"Chest"},{"key":"2025032409164329100_r28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1084\/jem.20101387","article-title":"Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon","volume":"209","author":"Rivollier","year":"2012","journal-title":"J. Exp. Med."},{"key":"2025032409164329100_r29","doi-asserted-by":"crossref","first-page":"e4204","DOI":"10.1371\/journal.pone.0004204","article-title":"Respiratory dendritic cell subsets differ in their capacity to support the induction of virus-specific cytotoxic CD8+ T cell responses","volume":"4","author":"Kim","year":"2009","journal-title":"PLoS ONE"},{"key":"2025032409164329100_r30","first-page":"657","article-title":"Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for the effective inhibition of pulmonary cell-mediated immunity","volume":"148","author":"MacLean","year":"1996","journal-title":"Am. J. Pathol."},{"key":"2025032409164329100_r31","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.4049\/jimmunol.175.3.1884","article-title":"The inflammatory versus constitutive trafficking of mononuclear phagocytes into the alveolar space of mice is associated with drastic changes in their gene expression profiles","volume":"175","author":"Srivastava","year":"2005","journal-title":"J. Immunol."},{"key":"2025032409164329100_r32","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"2025032409164329100_r33","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1471-4906(02)02302-5","article-title":"Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes","volume":"23","author":"Mantovani","year":"2002","journal-title":"Trends Immunol."},{"key":"2025032409164329100_r34","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1465-9921-9-53","article-title":"Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice","volume":"9","author":"Gualano","year":"2008","journal-title":"Respir. Res."},{"key":"2025032409164329100_r35","doi-asserted-by":"crossref","first-page":"e8072","DOI":"10.1371\/journal.pone.0008072","article-title":"Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages","volume":"4","author":"Lee","year":"2009","journal-title":"PLoS ONE"},{"key":"2025032409164329100_r36","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/ni.1671","article-title":"Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens","volume":"9","author":"El Kasmi","year":"2008","journal-title":"Nat. Immunol."},{"key":"2025032409164329100_r37","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1084\/jem.188.8.1541","article-title":"Rapid interferon gamma-dependent clearance of influenza A virus and protection from consolidating pneumonitis in nitric oxide synthase 2-deficient mice","volume":"188","author":"Karupiah","year":"1998","journal-title":"J. Exp. Med."},{"key":"2025032409164329100_r38","doi-asserted-by":"crossref","first-page":"23301","DOI":"10.1016\/S0021-9258(18)50091-0","article-title":"Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10","volume":"267","author":"Bogdan","year":"1992","journal-title":"J. Biol. Chem."},{"key":"2025032409164329100_r39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nm.1929","article-title":"Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10","volume":"15","author":"Sun","year":"2009","journal-title":"Nat. Med."},{"key":"2025032409164329100_r40","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1164\/ajrccm.164.3.2007149","article-title":"Amplification of inflammation in emphysema and its association with latent adenoviral infection","volume":"164","author":"Retamales","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025032409164329100_r41","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1126\/science.277.5334.2002","article-title":"Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice","volume":"277","author":"Hautamaki","year":"1997","journal-title":"Science"},{"key":"2025032409164329100_r42","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1172\/JCI10458","article-title":"Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema","volume":"106","author":"Zheng","year":"2000","journal-title":"J. Clin. Invest."},{"key":"2025032409164329100_r43","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1056\/NEJMoa0904006","article-title":"MMP12, lung function, and COPD in high-risk populations","volume":"361","author":"Hunninghake","year":"2009","journal-title":"N. Engl. J. Med."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/2\/946\/62480845\/1200660.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/2\/946\/62480845\/1200660.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T04:06:06Z","timestamp":1743048366000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/189\/2\/946\/7989649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,7,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1200660","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,7]]},"published":{"date-parts":[[2012,7]]}}}