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Different recombinant Spikes might display different effects in vitro, according to protein length and glycosylation, and endotoxin (lipopolysaccharide, LPS) contamination.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>To assess (1) the effects of different Spikes on human primary M\u03a6 inflammation; (2) whether LPS contamination of recombinant Spike is (con)cause in vitro of increased M\u03a6 inflammation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Human primary M\u03a6 were incubated in the presence\/absence of several different Spikes (10\u00a0nM) or graded concentrations of LPS. Pro-inflammatory marker expression (qPCR and ELISA) and supernatant endotoxin contamination (LAL test) were the main readouts.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>LPS-free, glycosylated Spike (the form expressed in infected humans) caused no inflammation in  human primary M\u03a6. Two (out of five) Spikes were contaminated with endotoxins\u2009\u2265\u20093 EU\/ml and triggered inflammation. A non-contaminated non-glycosylated Spike produced in <jats:italic>E. coli<\/jats:italic> induced M\u03a6 inflammation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Glycosylated Spike per se is not pro-inflammatory for human M\u03a6, a feature which may be crucial to evade the host innate immunity. In vitro studies with commercially available Spike should be conducted with excruciating attention to potential LPS contamination.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s10565-021-09693-y","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T12:03:04Z","timestamp":1641902584000},"page":"667-678","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["SARS-CoV-2 Spike protein is not pro-inflammatory in human primary macrophages: endotoxin contamination and lack of protein glycosylation as possible confounders"],"prefix":"10.1007","volume":"38","author":[{"given":"Gloria","family":"Cinquegrani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Spigoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas Thomas","family":"Iannozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Parello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-1005","authenticated-orcid":false,"given":"Riccardo C.","family":"Bonadonna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Dei Cas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"issue":"7","key":"9693_CR1","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1093\/GLYCOB\/CWY021","volume":"28","author":"I Bagdonaite","year":"2018","unstructured":"Bagdonaite I, Wandall HH. 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ADC is an invited speaker for MSD, Astra Zeneca, Sanofi, Eli Lilly Ltd, Doc Generici, and Servier. All other authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}