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Recently, we have described that after engulfing hemoglobin (Hb)\u2010activated platelets, classical monocytes differentiated into pro\u2010inflammatory phenotypes, which were abundant in the circulation of paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease patients. Our current study shows that upon engulfment of Hb\u2010activated platelets, monocytes differentiate into M1\u2010macrophages under M1\u2010polarization stimulus (GM\u2010CSF, IFN\u2010\u03b3 + LPS). When grown under M2\u2010polarization stimulus (M\u2010CSF, IL\u20104 + IL13), the cells exhibited an M1\u2010like phenotype, secreted elevated levels of pro\u2010inflammatory cytokines including TNF\u2010\u03b1 and IL\u20101\u03b2, and displayed loss of the secretion of cytokine such as IL\u201010 and also phagocytic ability unlike the conventional M2 macrophages. Interestingly, when differentiated under the above polarization stimulus, monocytes from PNH patients expressed high levels of CD80 and phospho\u2010STAT1, like M1 macrophages. Hemolytic mice also exhibited a gradual increase in monocyte\u2013platelet aggregates in circulation and accumulation of CD80<jats:sup>high<\/jats:sup> macrophages in thioglycollate\u2010induced inflamed peritoneum. The spleen of the mice was also populated by CD80<jats:sup>high<\/jats:sup> macrophages with compromised phagocytic capacity. Our findings suggest that the hemolytic environment and specifically the Hb\u2010activated platelets, which are abundant in circulation during intravascular hemolysis, closely regulate monocyte differentiation.<\/jats:p>","DOI":"10.1002\/eji.201747449","type":"journal-article","created":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T17:30:50Z","timestamp":1524245450000},"page":"1285-1294","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Engulfment of Hb\u2010activated platelets differentiates monocytes into pro\u2010inflammatory macrophages in PNH patients"],"prefix":"10.1002","volume":"48","author":[{"given":"Rashi","family":"Singhal","sequence":"first","affiliation":[{"name":"Disease Biology Laboratory Regional Centre for Biotechnology  National Capital Region Biotech Science Cluster Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetal","family":"Chawla","sequence":"additional","affiliation":[{"name":"Disease Biology Laboratory Regional Centre for Biotechnology  National Capital Region Biotech Science Cluster Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harish","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Medicine All India Institute of Medical Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Gupta","sequence":"additional","affiliation":[{"name":"Disease Biology Laboratory Regional Centre for Biotechnology  National Capital Region Biotech Science Cluster Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Ojha","sequence":"additional","affiliation":[{"name":"Disease Biology Laboratory Regional Centre for Biotechnology  National Capital Region Biotech Science Cluster Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak K.","family":"Rathore","sequence":"additional","affiliation":[{"name":"Translational Health Science and Technology Institute  National Capital Region Biotech Science Cluster Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tulika","family":"Seth","sequence":"additional","affiliation":[{"name":"Department of Medicine All India Institute of Medical Sciences  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6601-6692","authenticated-orcid":false,"given":"Prasenjit","family":"Guchhait","sequence":"additional","affiliation":[{"name":"Disease Biology Laboratory Regional Centre for Biotechnology  National Capital Region Biotech Science Cluster Faridabad Haryana India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170355"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-403386"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.02.016"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.12.001"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.04.004"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.004"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.08.006"},{"key":"e_1_2_7_9_1","first-page":"1475435","article-title":"Monocyte heterogeneity: consequences for monocyte\u2010derived immune cells","author":"Sprangers S.","year":"2016","journal-title":"J. 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