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However, the mechanisms by which these phenotypic shifts occur have not yet been fully elucidated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The effects of oxLDL (1-40 \u03bcg\/ml; 24 h) on several parameters relevant to the Unfolded Protein Response (UPR)-mediated lipotoxic effects of oxLDL (disruption of ER Ca<jats:sup>2+<\/jats:sup> handling; activation of the UPR transcription factor XBP-1; upregulation of the UPR target genes BiP and CHOP; apoptosis; cell viability) were investigated in human primary monocyte-derived macrophages, and also in monocyte-macrophages derived from the THP-1 monocytic cell line. A consistent pattern was observed: M2-polarised macrophages were more sensitive to the lipotoxic effects of oxLDL than either non-polarised macrophages or non-differentiated monocytic cells. Specifically, M2-polarised macrophages were the only cell type to undergo significantly increased apoptosis (Primary cells: 1.23 \u00b1 0.01 basal; THP-1-derived: 1.97 \u00b1 0.12 basal; <jats:italic>P<\/jats:italic> &lt; 0.05 in both cases) and decreased cell viability (Primary cells: 0.79 \u00b1 0.04 basal; THP-1-derived: 0.67 \u00b1 0.02 basal; <jats:italic>P<\/jats:italic> &lt; 0.05 in both cases) when exposed to oxLDL levels similar to those seen in overweight individuals (ie. 1 \u03bcg\/ml).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We propose that the enhanced susceptibility of M2-polarised macrophages to lipotoxicity seen in the present <jats:italic>in vitro<\/jats:italic> study could, over time, contribute to the phenotypic shift seen in obese individuals <jats:italic>in vivo<\/jats:italic>. This is because a higher degree of oxLDL-induced lipotoxic cell death within M2 macrophages could contribute to a decrease in numbers of M2 cells, and thus a relative increase in proportion of non-M2 cells, within macrophage populations. Given the pro-inflammatory characteristics of a predominantly M1-polarised state, the data presented here may constitute a useful contribution to our understanding of the origin of the pro-inflammatory nature of obesity, and of the pathogenesis of obesity-associated inflammatory disorders such as Type 2 Diabetes and atherosclerosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1476-511x-10-229","type":"journal-article","created":{"date-parts":[[2011,12,6]],"date-time":"2011-12-06T19:26:42Z","timestamp":1323199602000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["M2 macrophages exhibit higher sensitivity to oxLDL-induced lipotoxicity than other monocyte\/macrophage subtypes"],"prefix":"10.1186","volume":"10","author":[{"given":"Suleiman A","family":"Isa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 S","family":"Ruffino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maninder","family":"Ahluwalia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew W","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Webb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,12,6]]},"reference":[{"issue":"19","key":"642_CR1","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1001\/jama.299.19.2287","volume":"299","author":"P Holvoet","year":"2008","unstructured":"Holvoet P, Lee D, Steffes M, Gross M, Jacobs DR: Association between Circulating Oxidised low-density lipoprotein and incidence of the metabolic syndrome. 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