{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:08:13Z","timestamp":1773407293478,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,5,27]],"date-time":"2014-05-27T00:00:00Z","timestamp":1401148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Hemophagocytes (HPCs) are activated macrophages that have engulfed other hematopoietic cells. Although HPCs are rarely identified in normal spleen tissue and bone marrow, an excess of these macrophages characterizes many cytokine storm syndromes, particularly macrophage activation syndrome and hemophagocytic lymphohistiocytosis. This study was undertaken to assess the functions of HPCs and their significance in acute inflammatory conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HPCs were generated in wild\u2010type mice using repeated stimulation with Toll\u2010like receptor 9 (TLR\u20109) and interleukin\u201010 receptor blockade. RNA was extracted from HPCs that had been isolated by laser\u2010captured microdissection. Transcriptional profiles of the HPCs were then compared to those of resting splenic macrophages. In addition, bone marrow samples were obtained from a diverse cohort of patients in whom excess hemophagocytosis was identified by clinical bone marrow biopsy or aspiration. The bone marrow samples were analyzed by immunohistochemistry for markers of classic (CD64) or alternative (CD163 and CD206) macrophage activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Differential gene expression and gene set enrichment analyses of murine HPCs identified up\u2010regulation of genes and gene sets associated with alternative activation of HPCs. Immunohistochemical analyses of HPCs in human bone marrow samples showed universal staining of HPCs for CD163, but rarely for CD206 or CD64.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Laser\u2010captured murine TLR\u20109\u2013induced HPCs had a transcriptional profile similar to that of alternatively activated macrophages. In addition, HPC expression of CD163 was confirmed in a uniquely diverse cohort of patients with hemophagocytic syndromes. Collectively, these data support the hypothesis that HPCs have both immunoregulatory and clean\u2010up functions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38379","type":"journal-article","created":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T14:25:27Z","timestamp":1390832727000},"page":"1666-1671","source":"Crossref","is-referenced-by-count":18,"title":["Brief Report: Alternative Activation of Laser\u2010Captured Murine Hemophagocytes"],"prefix":"10.1002","volume":"66","author":[{"given":"Scott W.","family":"Canna","sequence":"first","affiliation":[{"name":"National Institute for Arthritis and Musculoskeletal and Skin Diseases, NIH Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patr\u00edcia","family":"Costa\u2010Reis","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William E.","family":"Bernal","sequence":"additional","affiliation":[{"name":"University of California San Francisco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niansheng","family":"Chu","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen E.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia and University of Pennsylvania Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele E.","family":"Paessler","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia and University of Pennsylvania Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward M.","family":"Behrens","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia and University of Pennsylvania Philadelphia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,5,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32834dd37e"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20102538"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-2997"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.06.019"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37958"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/4.2.249"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-3050"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000247067.34173.1b"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22981"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-11-318832"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.016"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-276733"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38379","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38379","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:32:44Z","timestamp":1759941164000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.38379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,27]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1002\/art.38379"],"URL":"https:\/\/doi.org\/10.1002\/art.38379","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,27]]}}}