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Article: Effect of anti-neutrophil cytoplasm autoantibodies on the intracellular calcium concentration of human neutrophils

TitleEffect of anti-neutrophil cytoplasm autoantibodies on the intracellular calcium concentration of human neutrophils
Authors
KeywordsCalcium ionophore
Intracellular cytosolic-free calcium concentration
Platelet-activating factor
Systemic vasculitis
Issue Date1994
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/labinvest/
Citation
Laboratory Investigation, 1994, v. 70 n. 2, p. 152-162 How to Cite?
AbstractBACKGROUND: The discovery of circulating autoantibodies to neutrophil cytoplasm antigens (ANCA) has implicated autoimmune mechanisms in the pathogenesis of systemic vasculitis although it is uncertain whether these play a primary role or arise secondary to neutrophil injury. EXPERIMENTAL DESIGN: We examined the pathophysiologic effect of ANCA on intracellular cytosolic-free calcium concentration (Ca 2+)(i) in neutrophils by preincubating cells with ANCA-positive IgG or F(ab') 2 preparations followed by stimulation with calcium ionophore (A23187). The mechanism by which ANCA may affect (Ca 2+)(i) was studied by analyzing the production of platelet- activating factor (PAF), an intracellular messenger which is the mediator through which A23187 acts. RESULTS: ANCA-positive F(ab') 2 induced a small but insignificant increase in (Ca 2+)(i). Preincubation of neutrophils with ANCA-positive IgG or F(ab') 2 reduced the calcium mobilization induced by subsequent stimulation with A23187 compared with experiments performed with antibody preparations from ANCA-negative disease or healthy controls. The suppression of A23187-induced calcium mobilization was dose-dependent and correlated with the serum ANCA levels at clinical presentation. ANCA did not bind PAF but reduced the binding of PAF to neutrophils, suggesting that ANCA may prevent the expression of PAF receptor on activated neutrophils. The preincubation of neutrophils with increasing concentrations of F(ab') 2 preparation resulted in reduced membrane and supernatant concentrations of PAF, an effect that was more prominent with ANCA positive F(ab') 2. CONCLUSIONS: Our data suggest ANCA may potentially mediate a pathophysiologic effect on neutrophils through interference with the signal transduction pathways utilized in neutrophils activation. One of the possible mechanisms underlying the suppressive effect of ANCA on A23187-induced calcium mobilization may be mediated through the reduction of PAF synthesis.
Persistent Identifierhttp://hdl.handle.net/10722/162046
ISSN
2015 Impact Factor: 4.202
2015 SCImago Journal Rankings: 2.133
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKar Neng Laien_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorRifkin, Ien_HK
dc.contributor.authorLockwood, CMen_HK
dc.date.accessioned2012-09-05T05:16:53Z-
dc.date.available2012-09-05T05:16:53Z-
dc.date.issued1994en_HK
dc.identifier.citationLaboratory Investigation, 1994, v. 70 n. 2, p. 152-162en_HK
dc.identifier.issn0023-6837en_HK
dc.identifier.urihttp://hdl.handle.net/10722/162046-
dc.description.abstractBACKGROUND: The discovery of circulating autoantibodies to neutrophil cytoplasm antigens (ANCA) has implicated autoimmune mechanisms in the pathogenesis of systemic vasculitis although it is uncertain whether these play a primary role or arise secondary to neutrophil injury. EXPERIMENTAL DESIGN: We examined the pathophysiologic effect of ANCA on intracellular cytosolic-free calcium concentration (Ca 2+)(i) in neutrophils by preincubating cells with ANCA-positive IgG or F(ab') 2 preparations followed by stimulation with calcium ionophore (A23187). The mechanism by which ANCA may affect (Ca 2+)(i) was studied by analyzing the production of platelet- activating factor (PAF), an intracellular messenger which is the mediator through which A23187 acts. RESULTS: ANCA-positive F(ab') 2 induced a small but insignificant increase in (Ca 2+)(i). Preincubation of neutrophils with ANCA-positive IgG or F(ab') 2 reduced the calcium mobilization induced by subsequent stimulation with A23187 compared with experiments performed with antibody preparations from ANCA-negative disease or healthy controls. The suppression of A23187-induced calcium mobilization was dose-dependent and correlated with the serum ANCA levels at clinical presentation. ANCA did not bind PAF but reduced the binding of PAF to neutrophils, suggesting that ANCA may prevent the expression of PAF receptor on activated neutrophils. The preincubation of neutrophils with increasing concentrations of F(ab') 2 preparation resulted in reduced membrane and supernatant concentrations of PAF, an effect that was more prominent with ANCA positive F(ab') 2. CONCLUSIONS: Our data suggest ANCA may potentially mediate a pathophysiologic effect on neutrophils through interference with the signal transduction pathways utilized in neutrophils activation. One of the possible mechanisms underlying the suppressive effect of ANCA on A23187-induced calcium mobilization may be mediated through the reduction of PAF synthesis.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/labinvest/en_HK
dc.relation.ispartofLaboratory Investigationen_HK
dc.subjectCalcium ionophoreen_HK
dc.subjectIntracellular cytosolic-free calcium concentrationen_HK
dc.subjectPlatelet-activating factoren_HK
dc.subjectSystemic vasculitisen_HK
dc.subject.meshAntibodies, Antineutrophil Cytoplasmicen_US
dc.subject.meshAutoantibodies - Physiologyen_US
dc.subject.meshCalcimycin - Pharmacologyen_US
dc.subject.meshCalcium - Blooden_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin G - Physiologyen_US
dc.subject.meshKineticsen_US
dc.subject.meshNeutrophils - Metabolismen_US
dc.subject.meshPlatelet Activating Factor - Biosynthesisen_US
dc.subject.meshPolyarteritis Nodosa - Immunologyen_US
dc.subject.meshWegener Granulomatosis - Immunologyen_US
dc.titleEffect of anti-neutrophil cytoplasm autoantibodies on the intracellular calcium concentration of human neutrophilsen_HK
dc.typeArticleen_HK
dc.identifier.emailKar Neng Lai: knlai@hku.hken_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.authorityKar Neng Lai=rp00324en_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid7908069-
dc.identifier.scopuseid_2-s2.0-0028264814en_HK
dc.identifier.volume70en_HK
dc.identifier.issue2en_HK
dc.identifier.spage152en_HK
dc.identifier.epage162en_HK
dc.identifier.isiWOS:A1994NB69100003-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridKar Neng Lai=7402135706en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridRifkin, I=6602726351en_HK
dc.identifier.scopusauthoridLockwood, CM=35402271000en_HK

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