{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:52:52Z","timestamp":1790700772004,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Barbados Diabetes Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Inflammation"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>Intraplaque hemorrhage causes adaptive remodelling of macrophages towards a protective phenotype specialized towards handling iron and lipid overload, denoted Mhem. The Mhem phenotype expresses elevated levels of hemoglobin (Hb) scavenger receptor, CD163, capable of endocytosing pro-oxidant free Hb complexed to acute phase protein haptoglobin (Hp). It is notable that individuals homozygous for the Hp 2 allele (a poorer antioxidant) are at increased risk of cardiovascular disease compared to the Hp 1 allele. In this study, we examined whether scavenging of polymorphic Hp:Hb complexes differentially generated downstream anti-inflammatory signals in cultured human macrophages culminating in interleukin (IL)-10 secretion. We describe an anti-inflammatory signalling pathway involving phosphatidylinositol-3-kinase activation upstream of Akt phosphorylation (pSer473Akt) and IL-10 secretion. The pathway is mediated specifically through CD163 and is blocked by anti-CD163 antibody or phagocytosis inhibitor. However, levels of pSer473Akt and IL-10 were significantly diminished when scavenging polymorphic Hp2-2:Hb complexes compared to Hp1-1:Hb complexes<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mrow><mml:mo stretchy=\"false\">(<\/mml:mo><mml:mrow><mml:mi>P<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn>0.05<\/mml:mn><\/mml:mrow><mml:mo stretchy=\"false\">)<\/mml:mo><\/mml:mrow><\/mml:math>. Impaired anti-inflammatory macrophage signaling through a CD163\/pAkt\/IL-10 axis may thus represent a possible Hp2-2 disease mechanism in atherosclerosis.<\/jats:p>","DOI":"10.1155\/2013\/980327","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T21:17:00Z","timestamp":1366751820000},"page":"1-7","source":"Crossref","is-referenced-by-count":28,"title":["Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163<sup>+<\/sup>Macrophages"],"prefix":"10.1155","volume":"2013","author":[{"given":"R. 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