{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:48:49Z","timestamp":1791276529803,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2005,10,1]],"date-time":"2005-10-01T00:00:00Z","timestamp":1128124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Potent TLR4-dependent cell activation by Gram-negative bacterial endotoxins depends on sequential endotoxin-protein and protein-protein interactions with LPS-binding protein, CD14, myeloid differentiation protein 2 (MD-2), and TLR4. Previous studies have suggested that reduced agonist potency of underacylated endotoxins (i.e., tetra- or penta- vs hexa-acylated) is determined by post-CD14 interactions. To better define the molecular basis of the differences in agonist potency of endotoxins differing in fatty acid acylation, we compared endotoxins (lipooligosaccharides (LOS)) from hexa-acylated wild-type (wt), penta-acylated mutant msbB meningococcal strains as well as tetra-acylated LOS generated by treatment of wt LOS with the deacylating enzyme, acyloxyacylhydrolase. To facilitate assay of endotoxin:protein and endotoxin:cell interactions, the endotoxins were purified after metabolic labeling with [3H]- or [14C]acetate. All LOS species tested formed monomeric complexes with MD-2 in an LPS-binding protein- and CD14-dependent manner with similar efficiency. However, msbB LOS:MD-2 and acyloxyacylhydrolase-treated LOS:MD-2 were at least 10-fold less potent in inducing TLR4-dependent cell activation than wt LOS:MD-2 and partially antagonized the action of wt LOS:MD-2. These findings suggest that underacylated endotoxins produce decreased TLR4-dependent cell activation by altering the interaction of the endotoxin:MD-2 complex with TLR4 in a way that reduces receptor activation. Differences in potency among these endotoxin species is determined not by different aggregate properties, but by different properties of monomeric endotoxin:MD-2 complexes.<\/jats:p>","DOI":"10.4049\/jimmunol.175.7.4669","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:55:01Z","timestamp":1398034501000},"page":"4669-4676","source":"Crossref","is-referenced-by-count":128,"title":["Molecular Basis of Reduced Potency of Underacylated Endotoxins"],"prefix":"10.1093","volume":"175","author":[{"given":"Athmane","family":"Teghanemt","sequence":"first","affiliation":[{"name":"Inflammation Program, Departments of Internal Medicine , Coralville, IA 52241"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DeSheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Inflammation Program, Departments of Internal Medicine , Coralville, IA 52241"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika N","family":"Levis","sequence":"additional","affiliation":[{"name":"Inflammation Program, Departments of Internal Medicine , Coralville, IA 52241"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerrold P","family":"Weiss","sequence":"additional","affiliation":[{"name":"Inflammation Program, Departments of Internal Medicine , Coralville, IA 52241"},{"name":"Department of Microbiology, Roy J. and Lucille A. 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