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Article: Characterization of two novel LPS-binding sites in leukocyte integrin βA domain

TitleCharacterization of two novel LPS-binding sites in leukocyte integrin βA domain
Authors
KeywordsEndotoxin-neutralizing peptide
Lipopolysaccharide
NF-κB
Prophylaxis
Sepsis
TNF-α
Issue Date2007
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
Faseb Journal, 2007, v. 21 n. 12, p. 3231-3239 How to Cite?
AbstractLipopolysaccharide (LPS), a bacterial endotoxin, triggers deleterious systemic inflammatory responses when released into blood circulation, causing organ dysfunction and death. In response to LPS stimulation, CD14 and toll-like receptor (TLR)-4 elicit inflammatory signaling cascades. Although leukocyte integrins (CD11b/CD18 and CD11c/CD18) were reported to bind LPS and induce NF-κB translocation, the evidence on such epitope location remains elusive. The present study aims to delineate the LPS-binding sites on the integrin CD18 antigen and to design peptide(s) as potential prophylactic and/or therapeutic agents to modulate LPS effects in activated Jurkat cells. Epitope mapping analysis using a series of CD18 truncated variants revealed two putative LPS-binding sites within the βA region (216-248 and 266-318 a.a.), which were further confirmed by point mutation studies. Inhibition assay demonstrated that the CD18-βA266-318 peptide could block LPS binding in a dosedependent manner. Our data also indicated that treatment with the CD18-peptide modulated TNF-α mRNA transcription via the NF-κB signaling pathway in LPS-activated Jurkat cells. In conclusion, we have identified two novel LPS-binding sites located at the CD18 βA domain of leukocyte integrin, and the integrin peptide βA266-318 is shown to inhibit LPS binding and subsequent inflammatory events, having therapeutic implications to cure Gram-negative endotoxemia. © FASEB.
Persistent Identifierhttp://hdl.handle.net/10722/172952
ISSN
2021 Impact Factor: 5.834
2020 SCImago Journal Rankings: 1.709
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, KFen_US
dc.contributor.authorLuk, JMen_US
dc.contributor.authorCheng, RHen_US
dc.contributor.authorKlickstein, LBen_US
dc.contributor.authorFan, STen_US
dc.date.accessioned2012-10-30T06:25:59Z-
dc.date.available2012-10-30T06:25:59Z-
dc.date.issued2007en_US
dc.identifier.citationFaseb Journal, 2007, v. 21 n. 12, p. 3231-3239en_US
dc.identifier.issn0892-6638en_US
dc.identifier.urihttp://hdl.handle.net/10722/172952-
dc.description.abstractLipopolysaccharide (LPS), a bacterial endotoxin, triggers deleterious systemic inflammatory responses when released into blood circulation, causing organ dysfunction and death. In response to LPS stimulation, CD14 and toll-like receptor (TLR)-4 elicit inflammatory signaling cascades. Although leukocyte integrins (CD11b/CD18 and CD11c/CD18) were reported to bind LPS and induce NF-κB translocation, the evidence on such epitope location remains elusive. The present study aims to delineate the LPS-binding sites on the integrin CD18 antigen and to design peptide(s) as potential prophylactic and/or therapeutic agents to modulate LPS effects in activated Jurkat cells. Epitope mapping analysis using a series of CD18 truncated variants revealed two putative LPS-binding sites within the βA region (216-248 and 266-318 a.a.), which were further confirmed by point mutation studies. Inhibition assay demonstrated that the CD18-βA266-318 peptide could block LPS binding in a dosedependent manner. Our data also indicated that treatment with the CD18-peptide modulated TNF-α mRNA transcription via the NF-κB signaling pathway in LPS-activated Jurkat cells. In conclusion, we have identified two novel LPS-binding sites located at the CD18 βA domain of leukocyte integrin, and the integrin peptide βA266-318 is shown to inhibit LPS binding and subsequent inflammatory events, having therapeutic implications to cure Gram-negative endotoxemia. © FASEB.en_US
dc.languageengen_US
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/en_US
dc.relation.ispartofFASEB Journalen_US
dc.subjectEndotoxin-neutralizing peptide-
dc.subjectLipopolysaccharide-
dc.subjectNF-κB-
dc.subjectProphylaxis-
dc.subjectSepsis-
dc.subjectTNF-α-
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntigens, Cd18 - Chemistry - Genetics - Metabolismen_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshHumansen_US
dc.subject.meshJurkat Cellsen_US
dc.subject.meshLeukocytes - Immunologyen_US
dc.subject.meshLipopolysaccharides - Metabolismen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshNf-Kappa B - Metabolismen_US
dc.subject.meshPeptides - Genetics - Metabolismen_US
dc.subject.meshPoint Mutationen_US
dc.subject.meshProtein Structure, Secondaryen_US
dc.subject.meshSequence Alignmenten_US
dc.subject.meshSignal Transduction - Physiologyen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Genetics - Metabolismen_US
dc.titleCharacterization of two novel LPS-binding sites in leukocyte integrin βA domainen_US
dc.typeArticleen_US
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_US
dc.identifier.emailFan, ST: stfan@hku.hken_US
dc.identifier.authorityLuk, JM=rp00349en_US
dc.identifier.authorityFan, ST=rp00355en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1096/fj.06-7579comen_US
dc.identifier.pmid17522381-
dc.identifier.scopuseid_2-s2.0-35248867073en_US
dc.identifier.hkuros138559-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-35248867073&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume21en_US
dc.identifier.issue12en_US
dc.identifier.spage3231en_US
dc.identifier.epage3239en_US
dc.identifier.isiWOS:000249781600023-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWong, KF=35081410800en_US
dc.identifier.scopusauthoridLuk, JM=7006777791en_US
dc.identifier.scopusauthoridCheng, RH=21033815200en_US
dc.identifier.scopusauthoridKlickstein, LB=7003850930en_US
dc.identifier.scopusauthoridFan, ST=7402678224en_US
dc.identifier.issnl0892-6638-

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