{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T16:37:07Z","timestamp":1782146227126,"version":"3.54.5"},"reference-count":42,"publisher":"European Respiratory Society (ERS)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2011,7,11]]},"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>Lung exposure to metal oxide nanoparticles (NPs) comprising soluble metal haptens may produce T-helper cell type 1 (Th1)- and Th17-associated delayed-type hypersensitivity (DTH) responses and pulmonary alveolar proteinosis (PAP).<\/jats:p><jats:p>In order to study this, haptenic metal oxide NPs (NiO, Co<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub>, Cr<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>and CuO) were instilled into the lungs of female Wistar rats, and the immunoinflammatory responses were assessed at 24 h and 4 weeks post-instillation. Primary culture of alveolar macrophages from Wistar rats was used to evaluate the effect of the NPs on the ability to clear surfactant.<\/jats:p><jats:p>NiO NPs induced chronic interstitial inflammation and pro-inflammatory Th1 and Th17 immune responses characterised by increases in the cytokines monocyte chemotactic protein (MCP)-1\/CCL2, interleukin (IL)-12 p40, interferon-\u03b3 and IL-17A, whilst similar pathological responses induced by Co<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub>NPs were associated with increases in MCP-1\/CCL2 and IL-12 p40. However, neither Cr<jats:sub>2<\/jats:sub>O<jats:sub>3<\/jats:sub>nor CuO NPs elicited immunoinflammatory reactions. PAP was induced by both NiO and Co<jats:sub>3<\/jats:sub>O<jats:sub>4<\/jats:sub>NPs during the chronic phase. PAP was associated with over-production of surfactant by proliferation of type II cells and impaired clearance of surfactant by macrophages.<\/jats:p><jats:p>These findings have implications for the risk management of occupational NP exposure and provide evidence that haptenic metal oxide NPs can induce chronic progressive lung immune responses<jats:italic>via<\/jats:italic>a DTH-like mechanism.<\/jats:p>","DOI":"10.1183\/09031936.00047111","type":"journal-article","created":{"date-parts":[[2011,8,5]],"date-time":"2011-08-05T00:54:50Z","timestamp":1312505690000},"page":"546-557","source":"Crossref","is-referenced-by-count":83,"title":["NiO and Co<sub>3<\/sub>O<sub>4<\/sub>nanoparticles induce lung DTH-like responses and alveolar 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