Loading…
Alkalinity of Neutrophil Phagocytic Vacuoles Is Modulated by HVCN1 and Has Consequences for Myeloperoxidase Activity: e0125906
The NADPH oxidase of neutrophils, essential for innate immunity, passes electrons across the phagocytic membrane to form superoxide in the phagocytic vacuole. Activity of the oxidase requires that charge movements across the vacuolar membrane are balanced. Using the pH indicator SNARF, we measured c...
Saved in:
Published in: | PloS one 2015-04, Vol.10 (4) |
---|---|
Main Authors: | , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | |
---|---|
cites | |
container_end_page | |
container_issue | 4 |
container_start_page | |
container_title | PloS one |
container_volume | 10 |
creator | Levine, Adam P Duchen, Michael R Villiers, Simon de Rich, Peter R Segal, Anthony W |
description | The NADPH oxidase of neutrophils, essential for innate immunity, passes electrons across the phagocytic membrane to form superoxide in the phagocytic vacuole. Activity of the oxidase requires that charge movements across the vacuolar membrane are balanced. Using the pH indicator SNARF, we measured changes in pH in the phagocytic vacuole and cytosol of neutrophils. In human cells, the vacuolar pH rose to ~9, and the cytosol acidified slightly. By contrast, in Hvcn1 knock out mouse neutrophils, the vacuolar pH rose above 11, vacuoles swelled, and the cytosol acidified excessively, demonstrating that ordinarily this channel plays an important role in charge compensation. Proton extrusion was not diminished in Hvcn1-/- mouse neutrophils arguing against its role in maintaining pH homeostasis across the plasma membrane. Conditions in the vacuole are optimal for bacterial killing by the neutral proteases, cathepsin G and elastase, and not by myeloperoxidase, activity of which was unphysiologically low at alkaline pH. |
doi_str_mv | 10.1371/journal.pone.0125906 |
format | article |
fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_1680447136</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1680447136</sourcerecordid><originalsourceid>FETCH-proquest_miscellaneous_16804471363</originalsourceid><addsrcrecordid>eNqVjr1OwzAURi0kJMrPGzDckaXBjlu3ZasiUBhaMaCulXFuqIvxDbk2IgvPToa-ANNZjs73CXGrZKH0Qt0fKffRhqKjiIVU5XwlzZmYqJUup6aU-kJcMh-lnOulMRPxuw4fNvjo0wDUwhZz6qk7-AAvB_tObkjewc66TAEZnhk21ORgEzbwNkC9q7YKbGygtgwVRcavjNGNaks9bAYM1GFPP76xjLB2yX-PSw-Ap2fX4ry1gfHmxCtx9_T4WtXTrqexxGn_6dlhCDYiZd4rs5Sz2UJpo_-h_gH19FnO</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1680447136</pqid></control><display><type>article</type><title>Alkalinity of Neutrophil Phagocytic Vacuoles Is Modulated by HVCN1 and Has Consequences for Myeloperoxidase Activity: e0125906</title><source>ProQuest - Publicly Available Content Database</source><source>PubMed Central</source><creator>Levine, Adam P ; Duchen, Michael R ; Villiers, Simon de ; Rich, Peter R ; Segal, Anthony W</creator><creatorcontrib>Levine, Adam P ; Duchen, Michael R ; Villiers, Simon de ; Rich, Peter R ; Segal, Anthony W</creatorcontrib><description>The NADPH oxidase of neutrophils, essential for innate immunity, passes electrons across the phagocytic membrane to form superoxide in the phagocytic vacuole. Activity of the oxidase requires that charge movements across the vacuolar membrane are balanced. Using the pH indicator SNARF, we measured changes in pH in the phagocytic vacuole and cytosol of neutrophils. In human cells, the vacuolar pH rose to ~9, and the cytosol acidified slightly. By contrast, in Hvcn1 knock out mouse neutrophils, the vacuolar pH rose above 11, vacuoles swelled, and the cytosol acidified excessively, demonstrating that ordinarily this channel plays an important role in charge compensation. Proton extrusion was not diminished in Hvcn1-/- mouse neutrophils arguing against its role in maintaining pH homeostasis across the plasma membrane. Conditions in the vacuole are optimal for bacterial killing by the neutral proteases, cathepsin G and elastase, and not by myeloperoxidase, activity of which was unphysiologically low at alkaline pH.</description><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0125906</identifier><language>eng</language><ispartof>PloS one, 2015-04, Vol.10 (4)</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958,37048</link.rule.ids></links><search><creatorcontrib>Levine, Adam P</creatorcontrib><creatorcontrib>Duchen, Michael R</creatorcontrib><creatorcontrib>Villiers, Simon de</creatorcontrib><creatorcontrib>Rich, Peter R</creatorcontrib><creatorcontrib>Segal, Anthony W</creatorcontrib><title>Alkalinity of Neutrophil Phagocytic Vacuoles Is Modulated by HVCN1 and Has Consequences for Myeloperoxidase Activity: e0125906</title><title>PloS one</title><description>The NADPH oxidase of neutrophils, essential for innate immunity, passes electrons across the phagocytic membrane to form superoxide in the phagocytic vacuole. Activity of the oxidase requires that charge movements across the vacuolar membrane are balanced. Using the pH indicator SNARF, we measured changes in pH in the phagocytic vacuole and cytosol of neutrophils. In human cells, the vacuolar pH rose to ~9, and the cytosol acidified slightly. By contrast, in Hvcn1 knock out mouse neutrophils, the vacuolar pH rose above 11, vacuoles swelled, and the cytosol acidified excessively, demonstrating that ordinarily this channel plays an important role in charge compensation. Proton extrusion was not diminished in Hvcn1-/- mouse neutrophils arguing against its role in maintaining pH homeostasis across the plasma membrane. Conditions in the vacuole are optimal for bacterial killing by the neutral proteases, cathepsin G and elastase, and not by myeloperoxidase, activity of which was unphysiologically low at alkaline pH.</description><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqVjr1OwzAURi0kJMrPGzDckaXBjlu3ZasiUBhaMaCulXFuqIvxDbk2IgvPToa-ANNZjs73CXGrZKH0Qt0fKffRhqKjiIVU5XwlzZmYqJUup6aU-kJcMh-lnOulMRPxuw4fNvjo0wDUwhZz6qk7-AAvB_tObkjewc66TAEZnhk21ORgEzbwNkC9q7YKbGygtgwVRcavjNGNaks9bAYM1GFPP76xjLB2yX-PSw-Ap2fX4ry1gfHmxCtx9_T4WtXTrqexxGn_6dlhCDYiZd4rs5Sz2UJpo_-h_gH19FnO</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Levine, Adam P</creator><creator>Duchen, Michael R</creator><creator>Villiers, Simon de</creator><creator>Rich, Peter R</creator><creator>Segal, Anthony W</creator><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20150401</creationdate><title>Alkalinity of Neutrophil Phagocytic Vacuoles Is Modulated by HVCN1 and Has Consequences for Myeloperoxidase Activity: e0125906</title><author>Levine, Adam P ; Duchen, Michael R ; Villiers, Simon de ; Rich, Peter R ; Segal, Anthony W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_16804471363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Levine, Adam P</creatorcontrib><creatorcontrib>Duchen, Michael R</creatorcontrib><creatorcontrib>Villiers, Simon de</creatorcontrib><creatorcontrib>Rich, Peter R</creatorcontrib><creatorcontrib>Segal, Anthony W</creatorcontrib><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Levine, Adam P</au><au>Duchen, Michael R</au><au>Villiers, Simon de</au><au>Rich, Peter R</au><au>Segal, Anthony W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alkalinity of Neutrophil Phagocytic Vacuoles Is Modulated by HVCN1 and Has Consequences for Myeloperoxidase Activity: e0125906</atitle><jtitle>PloS one</jtitle><date>2015-04-01</date><risdate>2015</risdate><volume>10</volume><issue>4</issue><eissn>1932-6203</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>content type line 23</notes><notes>ObjectType-Feature-2</notes><abstract>The NADPH oxidase of neutrophils, essential for innate immunity, passes electrons across the phagocytic membrane to form superoxide in the phagocytic vacuole. Activity of the oxidase requires that charge movements across the vacuolar membrane are balanced. Using the pH indicator SNARF, we measured changes in pH in the phagocytic vacuole and cytosol of neutrophils. In human cells, the vacuolar pH rose to ~9, and the cytosol acidified slightly. By contrast, in Hvcn1 knock out mouse neutrophils, the vacuolar pH rose above 11, vacuoles swelled, and the cytosol acidified excessively, demonstrating that ordinarily this channel plays an important role in charge compensation. Proton extrusion was not diminished in Hvcn1-/- mouse neutrophils arguing against its role in maintaining pH homeostasis across the plasma membrane. Conditions in the vacuole are optimal for bacterial killing by the neutral proteases, cathepsin G and elastase, and not by myeloperoxidase, activity of which was unphysiologically low at alkaline pH.</abstract><doi>10.1371/journal.pone.0125906</doi></addata></record> |
fulltext | fulltext |
identifier | EISSN: 1932-6203 |
ispartof | PloS one, 2015-04, Vol.10 (4) |
issn | 1932-6203 |
language | eng |
recordid | cdi_proquest_miscellaneous_1680447136 |
source | ProQuest - Publicly Available Content Database; PubMed Central |
title | Alkalinity of Neutrophil Phagocytic Vacuoles Is Modulated by HVCN1 and Has Consequences for Myeloperoxidase Activity: e0125906 |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T12%3A32%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Alkalinity%20of%20Neutrophil%20Phagocytic%20Vacuoles%20Is%20Modulated%20by%20HVCN1%20and%20Has%20Consequences%20for%20Myeloperoxidase%20Activity:%20e0125906&rft.jtitle=PloS%20one&rft.au=Levine,%20Adam%20P&rft.date=2015-04-01&rft.volume=10&rft.issue=4&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0125906&rft_dat=%3Cproquest%3E1680447136%3C/proquest%3E%3Cgrp_id%3Ecdi_FETCH-proquest_miscellaneous_16804471363%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1680447136&rft_id=info:pmid/&rfr_iscdi=true |