Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane

Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane. Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space....

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Kidney Int.; (United States) 1984-10, Vol.26 (4), p.397-403
Hauptverfasser: Madaio, Michael P., Salant, David J., Adler, Stephen, Darby, Christine, Couser, William G.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 403
container_issue 4
container_start_page 397
container_title Kidney Int.; (United States)
container_volume 26
creator Madaio, Michael P.
Salant, David J.
Adler, Stephen
Darby, Christine
Couser, William G.
description Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane. Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. We examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by comparing the rate of deposition of antibodies with cationic and anionic isoelectric points. Purified sheep anti-rat GBM IgG was isolated from acid eluates of kidneys obtained 24 hr after rats were injected with sheep antiserum to rat GBM. Anti-GBM IgG was separated into cationic (pI 6.4–8.5) and anionic (pI 4.2–6.8) fractions, which were radiolabelled with 131I and 125I, respectively, shown to have equal antibody contents measured by in vitro binding to normal glomeruli, mixed in equal amounts, and injected in incremental doses to ten rats. At 1 hr the glomerular antibody binding of each fraction was directly related to the blood level (r = 0.95, r = 0.97) and delivery of antibody (r = 0.98, r = 0.98). Glomerular binding of cationic antibody was four times greater than anionic antibody over the entire range of deliveries studied (P < 0.001). We conclude that glomerular deposition of anti-GBM antibody is directly related to blood concentration and delivery of antibody. Furthermore, the deposition of cationic antibodies to GBM antigens was significantly greater than the deposition of anionic antibodies. The charge-selective glomerular filtration barrier may be an important determinant of the quantity and subclass composition of anti-GBM IgG deposits in glomeruli, and therefore of the severity of tissue injury produced. Effet de la charge et de la concentration d'un anticorps sur le dépôt d'anticorps sur la membrane basale glomérulaire. Les sites anioniques fixes dans la paroi capillaire glomérulaire influencent le passage des protéines sériques, la localisation de divers antigènes et le dépôt d'anticorps dans l'espace sousépithélial. Dans la néphrite à anti-GBM, le dépôt d'anticorps survient très rapidement sur des sites antigéniques situés de façon relativement proximale dans la paroi capillaire glomérulaire. Nous avons examiné l'influence de la barriére de charge glomérulaire sur de dépôt d'anticorps anti-GBM en comparant la vi
doi_str_mv 10.1038/ki.1984.188
format Article
fullrecord <record><control><sourceid>proquest_osti_</sourceid><recordid>TN_cdi_proquest_miscellaneous_75884529</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S008525381533297X</els_id><sourcerecordid>75884529</sourcerecordid><originalsourceid>FETCH-LOGICAL-c423t-92180be933c9fab95730e5392f5799667d274559737c9303355a66a854bfa53e3</originalsourceid><addsrcrecordid>eNptkUFr3DAQhUVJSLZpTz0HTAm9FG8ky2NJxxKSNhDopTkLWR4lSmxrI2kL-feV8RJ6CAjEY74ZzXsi5AujW0a5vHz2W6Zku2VSfiAbBg2vmQA4IhtKJdQNcHlKPqb0RItWnJ6Qkw4a0Qq6IXjtHNpcBVeZOfs-DK-VfTTxAYseKhtmi3OOJvswV-UMuAvJr-q_lhyqhzFMGPejiVVvEk6lrZpw6qOZ8RM5dmZM-Plwn5H7m-s_V7_qu98_b69-3NW2bXiuVcMk7VFxbpUzvQLBKQJXjQOhVNeJoWwNoAQXtvjgHMB0nZHQ9s4AR35Gvq5zQ8peJ-sz2sfiYS4WNXQdVwIK9G2FdjG87DFlPflkcRzLomGftAApW2hUAb-voI0hpYhO76KfTHzVjOolef3s9ZK8LskX-vwwdt9POLyxh6hL_eJQN8ma0ZVcrE9vmGIgKSxjYMWw5PTXY1xsYPmFwcfFxRD8u8__AwaCnJM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>75884529</pqid></control><display><type>article</type><title>Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Madaio, Michael P. ; Salant, David J. ; Adler, Stephen ; Darby, Christine ; Couser, William G.</creator><creatorcontrib>Madaio, Michael P. ; Salant, David J. ; Adler, Stephen ; Darby, Christine ; Couser, William G. ; Boston Univ. Medical Center, MA</creatorcontrib><description>Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane. Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. We examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by comparing the rate of deposition of antibodies with cationic and anionic isoelectric points. Purified sheep anti-rat GBM IgG was isolated from acid eluates of kidneys obtained 24 hr after rats were injected with sheep antiserum to rat GBM. Anti-GBM IgG was separated into cationic (pI 6.4–8.5) and anionic (pI 4.2–6.8) fractions, which were radiolabelled with 131I and 125I, respectively, shown to have equal antibody contents measured by in vitro binding to normal glomeruli, mixed in equal amounts, and injected in incremental doses to ten rats. At 1 hr the glomerular antibody binding of each fraction was directly related to the blood level (r = 0.95, r = 0.97) and delivery of antibody (r = 0.98, r = 0.98). Glomerular binding of cationic antibody was four times greater than anionic antibody over the entire range of deliveries studied (P &lt; 0.001). We conclude that glomerular deposition of anti-GBM antibody is directly related to blood concentration and delivery of antibody. Furthermore, the deposition of cationic antibodies to GBM antigens was significantly greater than the deposition of anionic antibodies. The charge-selective glomerular filtration barrier may be an important determinant of the quantity and subclass composition of anti-GBM IgG deposits in glomeruli, and therefore of the severity of tissue injury produced. Effet de la charge et de la concentration d'un anticorps sur le dépôt d'anticorps sur la membrane basale glomérulaire. Les sites anioniques fixes dans la paroi capillaire glomérulaire influencent le passage des protéines sériques, la localisation de divers antigènes et le dépôt d'anticorps dans l'espace sousépithélial. Dans la néphrite à anti-GBM, le dépôt d'anticorps survient très rapidement sur des sites antigéniques situés de façon relativement proximale dans la paroi capillaire glomérulaire. Nous avons examiné l'influence de la barriére de charge glomérulaire sur de dépôt d'anticorps anti-GBM en comparant la vitesse de dépôt d'anticorps avec des points isoélectriques cationiques ou anioniques. De l'IgG purifiée de mouton anti-GBM de rat a été isolée à partir d'éluats acides de reins obtenus 24 heures après que les rats aient reçu des injections d'antisérum de mouton contre la GBM de rat. Les IgG anti-GBM ont été séparées en fractions cationiques (pI 6,4–8,5) et anioniques (pI 4,2–6,8) qui ont été radiomarquées avec 131I et 125I, respectivement, dont on a montré que le contenu anticorps était identique en le mesurant par leur liaison in vitro à des glomérules normaux, qui ont été mélangés en quantités égales et injectés é des doses croissantes à dix rats. Au bout d'une heure, la liaison glomérulaire de chaque fraction d'anticorps était directement liée à leur niveau sanguin (r = 0,95, r = 0,97), et à l'afflux d'anticorps (r = 0,98, r = 0,98). La liaison glomérulaire d'anticorps cationiques était quatre fois plus grande que celle des anticorps anioniques pour l'ensemble des afflux étudiés (P &lt; 0,001). Nous concluons que le dépôt glomérulaire d'anticorps anti-GBM est directement relié à la concentration sanguine et à l'afflux de l'anticorps. En outre, le dépôt d'anticorps cationiques sur les antigènes GBM était significativement plus élevé que le dépôt des anticorps anioniques. La barrière de filtration glomérulaire liée aux charges pourrait être un déterminant important de la quantité et de la composition des sous-classes des dépôts d'IgG anti-GBM dans les glomérules et donc de la sévérité de la lésion tissulaire provoquée.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1038/ki.1984.188</identifier><identifier>PMID: 6527470</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>551001 - Physiological Systems- Tracer Techniques ; ANIMALS ; ANIONS ; ANTIBODIES ; Antigen-Antibody Complex - immunology ; ANTIGEN-ANTIBODY REACTIONS ; ANTIGENS ; Antigens, Surface - immunology ; Basement Membrane - immunology ; BASIC BIOLOGICAL SCIENCES ; BETA DECAY RADIOISOTOPES ; BETA-MINUS DECAY RADIOISOTOPES ; Binding Sites, Antibody ; Biological and medical sciences ; BIOLOGICAL MATERIALS ; BLOOD ; BODY ; BODY FLUIDS ; Capillary Permeability ; CATIONS ; CELL CONSTITUENTS ; CELL MEMBRANES ; CHARGED PARTICLES ; CHEMICAL BONDS ; DAYS LIVING RADIOISOTOPES ; ELECTRON CAPTURE RADIOISOTOPES ; Glomerulonephritis ; Immunoglobulin G - immunology ; Immunoglobulin G - metabolism ; INTERMEDIATE MASS NUCLEI ; IODINE 125 ; IODINE 131 ; IODINE ISOTOPES ; Iodine Radioisotopes ; IONS ; ISOTOPE APPLICATIONS ; ISOTOPES ; Kidney Glomerulus - immunology ; Kidney Glomerulus - metabolism ; KIDNEYS ; LABELLED COMPOUNDS ; MAMMALS ; MATERIALS ; Medical sciences ; MEMBRANES ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; NUCLEI ; ODD-EVEN NUCLEI ; ORGANS ; PERMEABILITY ; RADIOISOTOPES ; RATS ; Rats, Inbred Strains ; RETENTION ; RODENTS ; TRACER TECHNIQUES ; VERTEBRATES</subject><ispartof>Kidney Int.; (United States), 1984-10, Vol.26 (4), p.397-403</ispartof><rights>1984 International Society of Nephrology</rights><rights>1985 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-92180be933c9fab95730e5392f5799667d274559737c9303355a66a854bfa53e3</citedby><cites>FETCH-LOGICAL-c423t-92180be933c9fab95730e5392f5799667d274559737c9303355a66a854bfa53e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=9158058$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6527470$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/5663975$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Madaio, Michael P.</creatorcontrib><creatorcontrib>Salant, David J.</creatorcontrib><creatorcontrib>Adler, Stephen</creatorcontrib><creatorcontrib>Darby, Christine</creatorcontrib><creatorcontrib>Couser, William G.</creatorcontrib><creatorcontrib>Boston Univ. Medical Center, MA</creatorcontrib><title>Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane</title><title>Kidney Int.; (United States)</title><addtitle>Kidney Int</addtitle><description>Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane. Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. We examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by comparing the rate of deposition of antibodies with cationic and anionic isoelectric points. Purified sheep anti-rat GBM IgG was isolated from acid eluates of kidneys obtained 24 hr after rats were injected with sheep antiserum to rat GBM. Anti-GBM IgG was separated into cationic (pI 6.4–8.5) and anionic (pI 4.2–6.8) fractions, which were radiolabelled with 131I and 125I, respectively, shown to have equal antibody contents measured by in vitro binding to normal glomeruli, mixed in equal amounts, and injected in incremental doses to ten rats. At 1 hr the glomerular antibody binding of each fraction was directly related to the blood level (r = 0.95, r = 0.97) and delivery of antibody (r = 0.98, r = 0.98). Glomerular binding of cationic antibody was four times greater than anionic antibody over the entire range of deliveries studied (P &lt; 0.001). We conclude that glomerular deposition of anti-GBM antibody is directly related to blood concentration and delivery of antibody. Furthermore, the deposition of cationic antibodies to GBM antigens was significantly greater than the deposition of anionic antibodies. The charge-selective glomerular filtration barrier may be an important determinant of the quantity and subclass composition of anti-GBM IgG deposits in glomeruli, and therefore of the severity of tissue injury produced. Effet de la charge et de la concentration d'un anticorps sur le dépôt d'anticorps sur la membrane basale glomérulaire. Les sites anioniques fixes dans la paroi capillaire glomérulaire influencent le passage des protéines sériques, la localisation de divers antigènes et le dépôt d'anticorps dans l'espace sousépithélial. Dans la néphrite à anti-GBM, le dépôt d'anticorps survient très rapidement sur des sites antigéniques situés de façon relativement proximale dans la paroi capillaire glomérulaire. Nous avons examiné l'influence de la barriére de charge glomérulaire sur de dépôt d'anticorps anti-GBM en comparant la vitesse de dépôt d'anticorps avec des points isoélectriques cationiques ou anioniques. De l'IgG purifiée de mouton anti-GBM de rat a été isolée à partir d'éluats acides de reins obtenus 24 heures après que les rats aient reçu des injections d'antisérum de mouton contre la GBM de rat. Les IgG anti-GBM ont été séparées en fractions cationiques (pI 6,4–8,5) et anioniques (pI 4,2–6,8) qui ont été radiomarquées avec 131I et 125I, respectivement, dont on a montré que le contenu anticorps était identique en le mesurant par leur liaison in vitro à des glomérules normaux, qui ont été mélangés en quantités égales et injectés é des doses croissantes à dix rats. Au bout d'une heure, la liaison glomérulaire de chaque fraction d'anticorps était directement liée à leur niveau sanguin (r = 0,95, r = 0,97), et à l'afflux d'anticorps (r = 0,98, r = 0,98). La liaison glomérulaire d'anticorps cationiques était quatre fois plus grande que celle des anticorps anioniques pour l'ensemble des afflux étudiés (P &lt; 0,001). Nous concluons que le dépôt glomérulaire d'anticorps anti-GBM est directement relié à la concentration sanguine et à l'afflux de l'anticorps. En outre, le dépôt d'anticorps cationiques sur les antigènes GBM était significativement plus élevé que le dépôt des anticorps anioniques. La barrière de filtration glomérulaire liée aux charges pourrait être un déterminant important de la quantité et de la composition des sous-classes des dépôts d'IgG anti-GBM dans les glomérules et donc de la sévérité de la lésion tissulaire provoquée.</description><subject>551001 - Physiological Systems- Tracer Techniques</subject><subject>ANIMALS</subject><subject>ANIONS</subject><subject>ANTIBODIES</subject><subject>Antigen-Antibody Complex - immunology</subject><subject>ANTIGEN-ANTIBODY REACTIONS</subject><subject>ANTIGENS</subject><subject>Antigens, Surface - immunology</subject><subject>Basement Membrane - immunology</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>BETA DECAY RADIOISOTOPES</subject><subject>BETA-MINUS DECAY RADIOISOTOPES</subject><subject>Binding Sites, Antibody</subject><subject>Biological and medical sciences</subject><subject>BIOLOGICAL MATERIALS</subject><subject>BLOOD</subject><subject>BODY</subject><subject>BODY FLUIDS</subject><subject>Capillary Permeability</subject><subject>CATIONS</subject><subject>CELL CONSTITUENTS</subject><subject>CELL MEMBRANES</subject><subject>CHARGED PARTICLES</subject><subject>CHEMICAL BONDS</subject><subject>DAYS LIVING RADIOISOTOPES</subject><subject>ELECTRON CAPTURE RADIOISOTOPES</subject><subject>Glomerulonephritis</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulin G - metabolism</subject><subject>INTERMEDIATE MASS NUCLEI</subject><subject>IODINE 125</subject><subject>IODINE 131</subject><subject>IODINE ISOTOPES</subject><subject>Iodine Radioisotopes</subject><subject>IONS</subject><subject>ISOTOPE APPLICATIONS</subject><subject>ISOTOPES</subject><subject>Kidney Glomerulus - immunology</subject><subject>Kidney Glomerulus - metabolism</subject><subject>KIDNEYS</subject><subject>LABELLED COMPOUNDS</subject><subject>MAMMALS</subject><subject>MATERIALS</subject><subject>Medical sciences</subject><subject>MEMBRANES</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>NUCLEI</subject><subject>ODD-EVEN NUCLEI</subject><subject>ORGANS</subject><subject>PERMEABILITY</subject><subject>RADIOISOTOPES</subject><subject>RATS</subject><subject>Rats, Inbred Strains</subject><subject>RETENTION</subject><subject>RODENTS</subject><subject>TRACER TECHNIQUES</subject><subject>VERTEBRATES</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1984</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkUFr3DAQhUVJSLZpTz0HTAm9FG8ky2NJxxKSNhDopTkLWR4lSmxrI2kL-feV8RJ6CAjEY74ZzXsi5AujW0a5vHz2W6Zku2VSfiAbBg2vmQA4IhtKJdQNcHlKPqb0RItWnJ6Qkw4a0Qq6IXjtHNpcBVeZOfs-DK-VfTTxAYseKhtmi3OOJvswV-UMuAvJr-q_lhyqhzFMGPejiVVvEk6lrZpw6qOZ8RM5dmZM-Plwn5H7m-s_V7_qu98_b69-3NW2bXiuVcMk7VFxbpUzvQLBKQJXjQOhVNeJoWwNoAQXtvjgHMB0nZHQ9s4AR35Gvq5zQ8peJ-sz2sfiYS4WNXQdVwIK9G2FdjG87DFlPflkcRzLomGftAApW2hUAb-voI0hpYhO76KfTHzVjOolef3s9ZK8LskX-vwwdt9POLyxh6hL_eJQN8ma0ZVcrE9vmGIgKSxjYMWw5PTXY1xsYPmFwcfFxRD8u8__AwaCnJM</recordid><startdate>198410</startdate><enddate>198410</enddate><creator>Madaio, Michael P.</creator><creator>Salant, David J.</creator><creator>Adler, Stephen</creator><creator>Darby, Christine</creator><creator>Couser, William G.</creator><general>Elsevier Inc</general><general>Nature Publishing</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>198410</creationdate><title>Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane</title><author>Madaio, Michael P. ; Salant, David J. ; Adler, Stephen ; Darby, Christine ; Couser, William G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-92180be933c9fab95730e5392f5799667d274559737c9303355a66a854bfa53e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1984</creationdate><topic>551001 - Physiological Systems- Tracer Techniques</topic><topic>ANIMALS</topic><topic>ANIONS</topic><topic>ANTIBODIES</topic><topic>Antigen-Antibody Complex - immunology</topic><topic>ANTIGEN-ANTIBODY REACTIONS</topic><topic>ANTIGENS</topic><topic>Antigens, Surface - immunology</topic><topic>Basement Membrane - immunology</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>BETA DECAY RADIOISOTOPES</topic><topic>BETA-MINUS DECAY RADIOISOTOPES</topic><topic>Binding Sites, Antibody</topic><topic>Biological and medical sciences</topic><topic>BIOLOGICAL MATERIALS</topic><topic>BLOOD</topic><topic>BODY</topic><topic>BODY FLUIDS</topic><topic>Capillary Permeability</topic><topic>CATIONS</topic><topic>CELL CONSTITUENTS</topic><topic>CELL MEMBRANES</topic><topic>CHARGED PARTICLES</topic><topic>CHEMICAL BONDS</topic><topic>DAYS LIVING RADIOISOTOPES</topic><topic>ELECTRON CAPTURE RADIOISOTOPES</topic><topic>Glomerulonephritis</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunoglobulin G - metabolism</topic><topic>INTERMEDIATE MASS NUCLEI</topic><topic>IODINE 125</topic><topic>IODINE 131</topic><topic>IODINE ISOTOPES</topic><topic>Iodine Radioisotopes</topic><topic>IONS</topic><topic>ISOTOPE APPLICATIONS</topic><topic>ISOTOPES</topic><topic>Kidney Glomerulus - immunology</topic><topic>Kidney Glomerulus - metabolism</topic><topic>KIDNEYS</topic><topic>LABELLED COMPOUNDS</topic><topic>MAMMALS</topic><topic>MATERIALS</topic><topic>Medical sciences</topic><topic>MEMBRANES</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>NUCLEI</topic><topic>ODD-EVEN NUCLEI</topic><topic>ORGANS</topic><topic>PERMEABILITY</topic><topic>RADIOISOTOPES</topic><topic>RATS</topic><topic>Rats, Inbred Strains</topic><topic>RETENTION</topic><topic>RODENTS</topic><topic>TRACER TECHNIQUES</topic><topic>VERTEBRATES</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Madaio, Michael P.</creatorcontrib><creatorcontrib>Salant, David J.</creatorcontrib><creatorcontrib>Adler, Stephen</creatorcontrib><creatorcontrib>Darby, Christine</creatorcontrib><creatorcontrib>Couser, William G.</creatorcontrib><creatorcontrib>Boston Univ. Medical Center, MA</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Kidney Int.; (United States)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Madaio, Michael P.</au><au>Salant, David J.</au><au>Adler, Stephen</au><au>Darby, Christine</au><au>Couser, William G.</au><aucorp>Boston Univ. Medical Center, MA</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane</atitle><jtitle>Kidney Int.; (United States)</jtitle><addtitle>Kidney Int</addtitle><date>1984-10</date><risdate>1984</risdate><volume>26</volume><issue>4</issue><spage>397</spage><epage>403</epage><pages>397-403</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane. Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. We examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by comparing the rate of deposition of antibodies with cationic and anionic isoelectric points. Purified sheep anti-rat GBM IgG was isolated from acid eluates of kidneys obtained 24 hr after rats were injected with sheep antiserum to rat GBM. Anti-GBM IgG was separated into cationic (pI 6.4–8.5) and anionic (pI 4.2–6.8) fractions, which were radiolabelled with 131I and 125I, respectively, shown to have equal antibody contents measured by in vitro binding to normal glomeruli, mixed in equal amounts, and injected in incremental doses to ten rats. At 1 hr the glomerular antibody binding of each fraction was directly related to the blood level (r = 0.95, r = 0.97) and delivery of antibody (r = 0.98, r = 0.98). Glomerular binding of cationic antibody was four times greater than anionic antibody over the entire range of deliveries studied (P &lt; 0.001). We conclude that glomerular deposition of anti-GBM antibody is directly related to blood concentration and delivery of antibody. Furthermore, the deposition of cationic antibodies to GBM antigens was significantly greater than the deposition of anionic antibodies. The charge-selective glomerular filtration barrier may be an important determinant of the quantity and subclass composition of anti-GBM IgG deposits in glomeruli, and therefore of the severity of tissue injury produced. Effet de la charge et de la concentration d'un anticorps sur le dépôt d'anticorps sur la membrane basale glomérulaire. Les sites anioniques fixes dans la paroi capillaire glomérulaire influencent le passage des protéines sériques, la localisation de divers antigènes et le dépôt d'anticorps dans l'espace sousépithélial. Dans la néphrite à anti-GBM, le dépôt d'anticorps survient très rapidement sur des sites antigéniques situés de façon relativement proximale dans la paroi capillaire glomérulaire. Nous avons examiné l'influence de la barriére de charge glomérulaire sur de dépôt d'anticorps anti-GBM en comparant la vitesse de dépôt d'anticorps avec des points isoélectriques cationiques ou anioniques. De l'IgG purifiée de mouton anti-GBM de rat a été isolée à partir d'éluats acides de reins obtenus 24 heures après que les rats aient reçu des injections d'antisérum de mouton contre la GBM de rat. Les IgG anti-GBM ont été séparées en fractions cationiques (pI 6,4–8,5) et anioniques (pI 4,2–6,8) qui ont été radiomarquées avec 131I et 125I, respectivement, dont on a montré que le contenu anticorps était identique en le mesurant par leur liaison in vitro à des glomérules normaux, qui ont été mélangés en quantités égales et injectés é des doses croissantes à dix rats. Au bout d'une heure, la liaison glomérulaire de chaque fraction d'anticorps était directement liée à leur niveau sanguin (r = 0,95, r = 0,97), et à l'afflux d'anticorps (r = 0,98, r = 0,98). La liaison glomérulaire d'anticorps cationiques était quatre fois plus grande que celle des anticorps anioniques pour l'ensemble des afflux étudiés (P &lt; 0,001). Nous concluons que le dépôt glomérulaire d'anticorps anti-GBM est directement relié à la concentration sanguine et à l'afflux de l'anticorps. En outre, le dépôt d'anticorps cationiques sur les antigènes GBM était significativement plus élevé que le dépôt des anticorps anioniques. La barrière de filtration glomérulaire liée aux charges pourrait être un déterminant important de la quantité et de la composition des sous-classes des dépôts d'IgG anti-GBM dans les glomérules et donc de la sévérité de la lésion tissulaire provoquée.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>6527470</pmid><doi>10.1038/ki.1984.188</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0085-2538
ispartof Kidney Int.; (United States), 1984-10, Vol.26 (4), p.397-403
issn 0085-2538
1523-1755
language eng
recordid cdi_proquest_miscellaneous_75884529
source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects 551001 - Physiological Systems- Tracer Techniques
ANIMALS
ANIONS
ANTIBODIES
Antigen-Antibody Complex - immunology
ANTIGEN-ANTIBODY REACTIONS
ANTIGENS
Antigens, Surface - immunology
Basement Membrane - immunology
BASIC BIOLOGICAL SCIENCES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
Binding Sites, Antibody
Biological and medical sciences
BIOLOGICAL MATERIALS
BLOOD
BODY
BODY FLUIDS
Capillary Permeability
CATIONS
CELL CONSTITUENTS
CELL MEMBRANES
CHARGED PARTICLES
CHEMICAL BONDS
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
Glomerulonephritis
Immunoglobulin G - immunology
Immunoglobulin G - metabolism
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE 131
IODINE ISOTOPES
Iodine Radioisotopes
IONS
ISOTOPE APPLICATIONS
ISOTOPES
Kidney Glomerulus - immunology
Kidney Glomerulus - metabolism
KIDNEYS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
Medical sciences
MEMBRANES
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
NUCLEI
ODD-EVEN NUCLEI
ORGANS
PERMEABILITY
RADIOISOTOPES
RATS
Rats, Inbred Strains
RETENTION
RODENTS
TRACER TECHNIQUES
VERTEBRATES
title Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T21%3A42%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_osti_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effect%20of%20antibody%20charge%20and%20concentration%20on%20deposition%20of%20antibody%20to%20glomerular%20basement%20membrane&rft.jtitle=Kidney%20Int.;%20(United%20States)&rft.au=Madaio,%20Michael%20P.&rft.aucorp=Boston%20Univ.%20Medical%20Center,%20MA&rft.date=1984-10&rft.volume=26&rft.issue=4&rft.spage=397&rft.epage=403&rft.pages=397-403&rft.issn=0085-2538&rft.eissn=1523-1755&rft.coden=KDYIA5&rft_id=info:doi/10.1038/ki.1984.188&rft_dat=%3Cproquest_osti_%3E75884529%3C/proquest_osti_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=75884529&rft_id=info:pmid/6527470&rft_els_id=S008525381533297X&rfr_iscdi=true