Expression of acute-phase cytokines, surfactant proteins, and epithelial apoptosis in small airways of human acute respiratory distress syndrome
Abstract Purpose Recent studies suggest a role for distal airway injury in acute respiratory distress syndrome (ARDS). The epithelium lining the small airways secretes a large number of molecules such as surfactant components and inflammatory mediators. There is little information on how these small...
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creator | Pires-Neto, Ruy Camargo, PhD Morales, Maina Maria Barbosa, PhD Lancas, Tatiana, PhD Inforsato, Nicole, MD Duarte, Maria Irma Seixas, PhD Amato, Marcelo Britto Passos, PhD de Carvalho, Carlos Roberto Ribeiro, PhD da Silva, Luiz Fernando Ferraz, PhD Mauad, Thais, PhD Dolhnikoff, Marisa, PhD |
description | Abstract Purpose Recent studies suggest a role for distal airway injury in acute respiratory distress syndrome (ARDS). The epithelium lining the small airways secretes a large number of molecules such as surfactant components and inflammatory mediators. There is little information on how these small airway secretory functions are altered in ARDS. Materials and Methods We studied the lungs of 31 patients with ARDS (Pa o2 /fraction of inspired oxygen ≤ 200, 45 ± 14 years, 16 men) and 11 controls (52 ± 16 years, 7 men) submitted to autopsy and quantified the expression of interleukin (IL) 6, IL-8, surfactant proteins (SP) A and SP-B in the epithelium of small airways using immunohistochemistry and image analysis. In addition, an index of airway epithelial apoptosis was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphatase nick-end labeling assay, caspase 3, and Fas/Fas ligand expression. The density of inflammatory cells expressing IL-6 and IL-8 within the small airway walls was also quantified. Results Acute respiratory distress syndrome airways showed an increase in the epithelial expression of IL-8 ( P = .006) and an increased density of inflammatory cells expressing IL-6 ( P = .004) and IL-8 ( P < .001) compared with controls. There were no differences in SP-A and SP-B epithelium expression or in epithelial apoptosis index between ARDS and controls. Conclusion Distal airways are involved in ARDS lung inflammation and show a high expression of proinflammatory interleukins in both airway epithelial and inflammatory cells. Apoptosis may not be a major mechanism of airway epithelial cell death in ARDS. |
doi_str_mv | 10.1016/j.jcrc.2012.05.013 |
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The epithelium lining the small airways secretes a large number of molecules such as surfactant components and inflammatory mediators. There is little information on how these small airway secretory functions are altered in ARDS. Materials and Methods We studied the lungs of 31 patients with ARDS (Pa o2 /fraction of inspired oxygen ≤ 200, 45 ± 14 years, 16 men) and 11 controls (52 ± 16 years, 7 men) submitted to autopsy and quantified the expression of interleukin (IL) 6, IL-8, surfactant proteins (SP) A and SP-B in the epithelium of small airways using immunohistochemistry and image analysis. In addition, an index of airway epithelial apoptosis was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphatase nick-end labeling assay, caspase 3, and Fas/Fas ligand expression. The density of inflammatory cells expressing IL-6 and IL-8 within the small airway walls was also quantified. Results Acute respiratory distress syndrome airways showed an increase in the epithelial expression of IL-8 ( P = .006) and an increased density of inflammatory cells expressing IL-6 ( P = .004) and IL-8 ( P < .001) compared with controls. There were no differences in SP-A and SP-B epithelium expression or in epithelial apoptosis index between ARDS and controls. Conclusion Distal airways are involved in ARDS lung inflammation and show a high expression of proinflammatory interleukins in both airway epithelial and inflammatory cells. Apoptosis may not be a major mechanism of airway epithelial cell death in ARDS.</description><identifier>ISSN: 0883-9441</identifier><identifier>EISSN: 1557-8615</identifier><identifier>DOI: 10.1016/j.jcrc.2012.05.013</identifier><identifier>PMID: 22835422</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acute-Phase Proteins - metabolism ; Apoptosis ; ARDS ; Case-Control Studies ; Critical Care ; Cytokines ; Cytokines - metabolism ; Female ; Humans ; Immunohistochemistry ; Interleukin-6 - metabolism ; Interleukin-8 - metabolism ; Lungs ; Male ; Middle Aged ; Proteins ; Pulmonary Surfactant-Associated Protein A - metabolism ; Pulmonary Surfactant-Associated Protein B - metabolism ; Pulmonary Surfactant-Associated Proteins - metabolism ; Respiratory distress syndrome ; Respiratory Distress Syndrome, Adult - pathology ; Respiratory epithelium ; Respiratory Mucosa - metabolism ; Retrospective Studies ; Rodents ; Studies ; Surfactant protein</subject><ispartof>Journal of critical care, 2013-02, Vol.28 (1), p.111.e9-111.e15</ispartof><rights>Elsevier Inc.</rights><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c516t-ff93d0ae6dd36a3c40b95272d4685aba8b84a1aa8df03fec5baba210ffc52b3e3</citedby><cites>FETCH-LOGICAL-c516t-ff93d0ae6dd36a3c40b95272d4685aba8b84a1aa8df03fec5baba210ffc52b3e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S088394411200175X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22835422$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pires-Neto, Ruy Camargo, PhD</creatorcontrib><creatorcontrib>Morales, Maina Maria Barbosa, PhD</creatorcontrib><creatorcontrib>Lancas, Tatiana, PhD</creatorcontrib><creatorcontrib>Inforsato, Nicole, MD</creatorcontrib><creatorcontrib>Duarte, Maria Irma Seixas, PhD</creatorcontrib><creatorcontrib>Amato, Marcelo Britto Passos, PhD</creatorcontrib><creatorcontrib>de Carvalho, Carlos Roberto Ribeiro, PhD</creatorcontrib><creatorcontrib>da Silva, Luiz Fernando Ferraz, PhD</creatorcontrib><creatorcontrib>Mauad, Thais, PhD</creatorcontrib><creatorcontrib>Dolhnikoff, Marisa, PhD</creatorcontrib><title>Expression of acute-phase cytokines, surfactant proteins, and epithelial apoptosis in small airways of human acute respiratory distress syndrome</title><title>Journal of critical care</title><addtitle>J Crit Care</addtitle><description>Abstract Purpose Recent studies suggest a role for distal airway injury in acute respiratory distress syndrome (ARDS). The epithelium lining the small airways secretes a large number of molecules such as surfactant components and inflammatory mediators. There is little information on how these small airway secretory functions are altered in ARDS. Materials and Methods We studied the lungs of 31 patients with ARDS (Pa o2 /fraction of inspired oxygen ≤ 200, 45 ± 14 years, 16 men) and 11 controls (52 ± 16 years, 7 men) submitted to autopsy and quantified the expression of interleukin (IL) 6, IL-8, surfactant proteins (SP) A and SP-B in the epithelium of small airways using immunohistochemistry and image analysis. In addition, an index of airway epithelial apoptosis was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphatase nick-end labeling assay, caspase 3, and Fas/Fas ligand expression. The density of inflammatory cells expressing IL-6 and IL-8 within the small airway walls was also quantified. Results Acute respiratory distress syndrome airways showed an increase in the epithelial expression of IL-8 ( P = .006) and an increased density of inflammatory cells expressing IL-6 ( P = .004) and IL-8 ( P < .001) compared with controls. There were no differences in SP-A and SP-B epithelium expression or in epithelial apoptosis index between ARDS and controls. Conclusion Distal airways are involved in ARDS lung inflammation and show a high expression of proinflammatory interleukins in both airway epithelial and inflammatory cells. Apoptosis may not be a major mechanism of airway epithelial cell death in ARDS.</description><subject>Acute-Phase Proteins - metabolism</subject><subject>Apoptosis</subject><subject>ARDS</subject><subject>Case-Control Studies</subject><subject>Critical Care</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Interleukin-6 - metabolism</subject><subject>Interleukin-8 - metabolism</subject><subject>Lungs</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Proteins</subject><subject>Pulmonary Surfactant-Associated Protein A - metabolism</subject><subject>Pulmonary Surfactant-Associated Protein B - metabolism</subject><subject>Pulmonary Surfactant-Associated Proteins - metabolism</subject><subject>Respiratory distress syndrome</subject><subject>Respiratory Distress Syndrome, Adult - pathology</subject><subject>Respiratory epithelium</subject><subject>Respiratory Mucosa - metabolism</subject><subject>Retrospective Studies</subject><subject>Rodents</subject><subject>Studies</subject><subject>Surfactant protein</subject><issn>0883-9441</issn><issn>1557-8615</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkk-L1TAUxYsoznP0C7iQgBsXtuZP0_aBCDKMf2DAhQruQprc8vKmTWpuqvZb-JFNeaPCLHQVOPzOudycWxSPGa0YZc2LY3U00VScMl5RWVEm7hQ7JmVbdg2Td4sd7TpR7uuanRUPEI-UslYIeb8447wTsuZ8V_y8_DFHQHTBkzAQbZYE5XzQCMSsKVw7D_ic4BIHbZL2icwxJHA-i9pbArNLBxidHomew5wCOiTOE5z0mCUXv-sVt-DDMml_iid53uyiTiGuxDpM23yCq7cxTPCwuDfoEeHRzXtefH5z-eniXXn14e37i9dXpZGsSeUw7IWlGhprRaOFqWm_l7zltm46qXvd9V2tmdadHagYwMg-i5zRYTCS9wLEefHslJsX-roAJjU5NDCO2kNYULG6qSWTTVf_H-WilZTTjmb06S30GJbo8yKZ4qITbSvbTPETZWJAjDCoObpJx1UxqrZq1VFt1aqtWkWlytVm05Ob6KWfwP6x_O4yAy9PAORv--YgKjQOvAHrIpikbHD_zn91y25G553R4zWsgH_3UJg96uN2XNttMb7dlfwifgH0I82F</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Pires-Neto, Ruy Camargo, PhD</creator><creator>Morales, Maina Maria Barbosa, PhD</creator><creator>Lancas, Tatiana, PhD</creator><creator>Inforsato, Nicole, MD</creator><creator>Duarte, Maria Irma Seixas, PhD</creator><creator>Amato, Marcelo Britto Passos, PhD</creator><creator>de Carvalho, Carlos Roberto Ribeiro, PhD</creator><creator>da Silva, Luiz Fernando Ferraz, PhD</creator><creator>Mauad, Thais, PhD</creator><creator>Dolhnikoff, Marisa, PhD</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K6X</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20130201</creationdate><title>Expression of acute-phase cytokines, surfactant proteins, and epithelial apoptosis in small airways of human acute respiratory distress syndrome</title><author>Pires-Neto, Ruy Camargo, PhD ; Morales, Maina Maria Barbosa, PhD ; Lancas, Tatiana, PhD ; Inforsato, Nicole, MD ; Duarte, Maria Irma Seixas, PhD ; Amato, Marcelo Britto Passos, PhD ; de Carvalho, Carlos Roberto Ribeiro, PhD ; da Silva, Luiz Fernando Ferraz, PhD ; Mauad, Thais, PhD ; Dolhnikoff, Marisa, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c516t-ff93d0ae6dd36a3c40b95272d4685aba8b84a1aa8df03fec5baba210ffc52b3e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute-Phase Proteins - metabolism</topic><topic>Apoptosis</topic><topic>ARDS</topic><topic>Case-Control Studies</topic><topic>Critical Care</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Interleukin-6 - metabolism</topic><topic>Interleukin-8 - metabolism</topic><topic>Lungs</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Proteins</topic><topic>Pulmonary Surfactant-Associated Protein A - metabolism</topic><topic>Pulmonary Surfactant-Associated Protein B - metabolism</topic><topic>Pulmonary Surfactant-Associated Proteins - metabolism</topic><topic>Respiratory distress syndrome</topic><topic>Respiratory Distress Syndrome, Adult - pathology</topic><topic>Respiratory epithelium</topic><topic>Respiratory Mucosa - metabolism</topic><topic>Retrospective Studies</topic><topic>Rodents</topic><topic>Studies</topic><topic>Surfactant protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pires-Neto, Ruy Camargo, PhD</creatorcontrib><creatorcontrib>Morales, Maina Maria Barbosa, PhD</creatorcontrib><creatorcontrib>Lancas, Tatiana, PhD</creatorcontrib><creatorcontrib>Inforsato, Nicole, MD</creatorcontrib><creatorcontrib>Duarte, Maria Irma Seixas, PhD</creatorcontrib><creatorcontrib>Amato, Marcelo Britto Passos, PhD</creatorcontrib><creatorcontrib>de Carvalho, Carlos Roberto Ribeiro, PhD</creatorcontrib><creatorcontrib>da Silva, Luiz Fernando Ferraz, PhD</creatorcontrib><creatorcontrib>Mauad, Thais, PhD</creatorcontrib><creatorcontrib>Dolhnikoff, Marisa, PhD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>British Nursing Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of critical care</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pires-Neto, Ruy Camargo, PhD</au><au>Morales, Maina Maria Barbosa, PhD</au><au>Lancas, Tatiana, PhD</au><au>Inforsato, Nicole, MD</au><au>Duarte, Maria Irma Seixas, PhD</au><au>Amato, Marcelo Britto Passos, PhD</au><au>de Carvalho, Carlos Roberto Ribeiro, PhD</au><au>da Silva, Luiz Fernando Ferraz, PhD</au><au>Mauad, Thais, PhD</au><au>Dolhnikoff, Marisa, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of acute-phase cytokines, surfactant proteins, and epithelial apoptosis in small airways of human acute respiratory distress syndrome</atitle><jtitle>Journal of critical care</jtitle><addtitle>J Crit Care</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>28</volume><issue>1</issue><spage>111.e9</spage><epage>111.e15</epage><pages>111.e9-111.e15</pages><issn>0883-9441</issn><eissn>1557-8615</eissn><abstract>Abstract Purpose Recent studies suggest a role for distal airway injury in acute respiratory distress syndrome (ARDS). The epithelium lining the small airways secretes a large number of molecules such as surfactant components and inflammatory mediators. There is little information on how these small airway secretory functions are altered in ARDS. Materials and Methods We studied the lungs of 31 patients with ARDS (Pa o2 /fraction of inspired oxygen ≤ 200, 45 ± 14 years, 16 men) and 11 controls (52 ± 16 years, 7 men) submitted to autopsy and quantified the expression of interleukin (IL) 6, IL-8, surfactant proteins (SP) A and SP-B in the epithelium of small airways using immunohistochemistry and image analysis. In addition, an index of airway epithelial apoptosis was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine-triphosphatase nick-end labeling assay, caspase 3, and Fas/Fas ligand expression. The density of inflammatory cells expressing IL-6 and IL-8 within the small airway walls was also quantified. Results Acute respiratory distress syndrome airways showed an increase in the epithelial expression of IL-8 ( P = .006) and an increased density of inflammatory cells expressing IL-6 ( P = .004) and IL-8 ( P < .001) compared with controls. There were no differences in SP-A and SP-B epithelium expression or in epithelial apoptosis index between ARDS and controls. Conclusion Distal airways are involved in ARDS lung inflammation and show a high expression of proinflammatory interleukins in both airway epithelial and inflammatory cells. Apoptosis may not be a major mechanism of airway epithelial cell death in ARDS.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22835422</pmid><doi>10.1016/j.jcrc.2012.05.013</doi><oa>free_for_read</oa></addata></record> |
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subjects | Acute-Phase Proteins - metabolism Apoptosis ARDS Case-Control Studies Critical Care Cytokines Cytokines - metabolism Female Humans Immunohistochemistry Interleukin-6 - metabolism Interleukin-8 - metabolism Lungs Male Middle Aged Proteins Pulmonary Surfactant-Associated Protein A - metabolism Pulmonary Surfactant-Associated Protein B - metabolism Pulmonary Surfactant-Associated Proteins - metabolism Respiratory distress syndrome Respiratory Distress Syndrome, Adult - pathology Respiratory epithelium Respiratory Mucosa - metabolism Retrospective Studies Rodents Studies Surfactant protein |
title | Expression of acute-phase cytokines, surfactant proteins, and epithelial apoptosis in small airways of human acute respiratory distress syndrome |
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