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Article: Charge-dependent binding of polymeric IgA 1 to human mesangial cells in IgA nephropathy

TitleCharge-dependent binding of polymeric IgA 1 to human mesangial cells in IgA nephropathy
Authors
KeywordsAnionic charge
Cell injury
Charge dependent IgA binding
Deposits of IgA
Glomerulonephritis
Kidney mesangial cells
Polycation
Issue Date2001
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ki/index.html
Citation
Kidney International, 2001, v. 59 n. 1, p. 277-285 How to Cite?
AbstractBackground. IgA nephropathy (IgAN) is characterized by raised serum IgA 1 and predominant mesangial IgA 1 deposits of polymeric nature. The mechanism of polymeric IgA 1 (pIgA 1) deposition in the kidney mesangium is poorly understood in IgAN. It has been suggested that increased sialic acid content and anionic charge of the pIgA 1 molecules may be operational in the IgA 1 deposition in human mesangial cells (HMCs). The present study examined the binding of pIgA 1 with different surface charges to HMCs. The binding characteristics of IgA 1 to HMCs in the presence of polycation (poly-n-lysine) or polyanion (heparin) were also investigated. Methods. IgA 1 was purified in sera from patients with IgAN and from healthy controls by jacalin affinity chromatography. IgA 1 was further separated into pIgA 1 and monomeric IgA 1 (mIgA 1 by fast protein liquid chromatography (FPLC). pIgA 1 or mIgA 1 with different net charges on their surface were resolved by ion exchange chromatography (IEC) with a Mono Q column. The binding characteristics of pIgA 1 and mIgA 1 to HMCs in the presence or absence of polycation or polyanion were examined by flow cytometry. Results. In patients with IgAN, the absolute amount of mIgA 1 and pIgA 1 is significantly higher than that of healthy controls (P < 0.001). There was significant increase in binding of pIgA 1 from patients with IgAN to HMC and cell lysate. pIgA 1 that interacted strongly with the ion exchanger also bound more to HMCs when compared with IgA 1 interacted weakly with the ion exchanger (P < 0.001). The anionic charged pIgA 1 from patients was significantly higher than that of healthy controls (P < 0.001). Preincubation with poly-L-lysine increased the binding of pIgA 1 to HMCs. The binding of pIgA 1 to HMCs was decreased by preincubation with heparin. Conclusions. The binding of IgA to HMCs is charge dependent. Polymeric IgA with the highest net negative charge binds more to HMCs. Preincubation with polyanion decreased the binding of polymeric IgA to HMCs. These results suggest an important role for anionic charge in IgA 1 deposition onto the kidney mesangial cells.
Persistent Identifierhttp://hdl.handle.net/10722/162513
ISSN
2015 Impact Factor: 7.683
2015 SCImago Journal Rankings: 3.181
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorTang, SCWen_HK
dc.contributor.authorMan Fai Lamen_HK
dc.contributor.authorTak Mao Chanen_HK
dc.contributor.authorKar Neng Laien_HK
dc.date.accessioned2012-09-05T05:20:39Z-
dc.date.available2012-09-05T05:20:39Z-
dc.date.issued2001en_HK
dc.identifier.citationKidney International, 2001, v. 59 n. 1, p. 277-285en_HK
dc.identifier.issn0085-2538en_HK
dc.identifier.urihttp://hdl.handle.net/10722/162513-
dc.description.abstractBackground. IgA nephropathy (IgAN) is characterized by raised serum IgA 1 and predominant mesangial IgA 1 deposits of polymeric nature. The mechanism of polymeric IgA 1 (pIgA 1) deposition in the kidney mesangium is poorly understood in IgAN. It has been suggested that increased sialic acid content and anionic charge of the pIgA 1 molecules may be operational in the IgA 1 deposition in human mesangial cells (HMCs). The present study examined the binding of pIgA 1 with different surface charges to HMCs. The binding characteristics of IgA 1 to HMCs in the presence of polycation (poly-n-lysine) or polyanion (heparin) were also investigated. Methods. IgA 1 was purified in sera from patients with IgAN and from healthy controls by jacalin affinity chromatography. IgA 1 was further separated into pIgA 1 and monomeric IgA 1 (mIgA 1 by fast protein liquid chromatography (FPLC). pIgA 1 or mIgA 1 with different net charges on their surface were resolved by ion exchange chromatography (IEC) with a Mono Q column. The binding characteristics of pIgA 1 and mIgA 1 to HMCs in the presence or absence of polycation or polyanion were examined by flow cytometry. Results. In patients with IgAN, the absolute amount of mIgA 1 and pIgA 1 is significantly higher than that of healthy controls (P < 0.001). There was significant increase in binding of pIgA 1 from patients with IgAN to HMC and cell lysate. pIgA 1 that interacted strongly with the ion exchanger also bound more to HMCs when compared with IgA 1 interacted weakly with the ion exchanger (P < 0.001). The anionic charged pIgA 1 from patients was significantly higher than that of healthy controls (P < 0.001). Preincubation with poly-L-lysine increased the binding of pIgA 1 to HMCs. The binding of pIgA 1 to HMCs was decreased by preincubation with heparin. Conclusions. The binding of IgA to HMCs is charge dependent. Polymeric IgA with the highest net negative charge binds more to HMCs. Preincubation with polyanion decreased the binding of polymeric IgA to HMCs. These results suggest an important role for anionic charge in IgA 1 deposition onto the kidney mesangial cells.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ki/index.htmlen_HK
dc.relation.ispartofKidney Internationalen_HK
dc.subjectAnionic chargeen_HK
dc.subjectCell injuryen_HK
dc.subjectCharge dependent IgA bindingen_HK
dc.subjectDeposits of IgAen_HK
dc.subjectGlomerulonephritisen_HK
dc.subjectKidney mesangial cellsen_HK
dc.subjectPolycationen_HK
dc.subject.meshAdulten_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshChromatography, Ion Exchangeen_US
dc.subject.meshElectrophysiologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGlomerular Mesangium - Metabolism - Pathologyen_US
dc.subject.meshGlomerulonephritis, Iga - Metabolism - Pathologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin A - Metabolismen_US
dc.subject.meshMaleen_US
dc.subject.meshPolymers - Metabolismen_US
dc.titleCharge-dependent binding of polymeric IgA 1 to human mesangial cells in IgA nephropathyen_HK
dc.typeArticleen_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailTang, SCW: scwtang@hku.hken_HK
dc.identifier.emailTak Mao Chan: dtmchan@hku.hken_HK
dc.identifier.emailKar Neng Lai: knlai@hku.hken_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityTang, SCW=rp00480en_HK
dc.identifier.authorityTak Mao Chan=rp00394en_HK
dc.identifier.authorityKar Neng Lai=rp00324en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1046/j.1523-1755.2001.00489.xen_HK
dc.identifier.pmid11135081-
dc.identifier.scopuseid_2-s2.0-0035161794en_HK
dc.identifier.hkuros61529-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035161794&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume59en_HK
dc.identifier.issue1en_HK
dc.identifier.spage277en_HK
dc.identifier.epage285en_HK
dc.identifier.isiWOS:000166294700031-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridTang, SCW=7403437082en_HK
dc.identifier.scopusauthoridMan Fai Lam=7409883381en_HK
dc.identifier.scopusauthoridTak Mao Chan=7402687700en_HK
dc.identifier.scopusauthoridKar Neng Lai=7402135706en_HK

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