Mononuclear phagocytes and airway epithelial cells: novel sources of matrix metalloproteinase-8 (MMP-8) in patients with idiopathic pulmonary fibrosis
Matrix metalloproteinase-8 (MMP-8) promotes lung fibrotic responses to bleomycin in mice. Although prior studies reported that MMP-8 levels are increased in plasma and bronchoalveolar lavage fluid (BALF) samples from IPF patients, neither the bioactive forms nor the cellular sources of MMP-8 in idio...
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| Veröffentlicht in: | PloS one 2014-05, Vol.9 (5), p.e97485-e97485 |
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| creator | Craig, Vanessa J Polverino, Francesca Laucho-Contreras, Maria E Shi, Yuanyuan Liu, Yushi Osorio, Juan C Tesfaigzi, Yohannes Pinto-Plata, Victor Gochuico, Bernadette R Rosas, Ivan O Owen, Caroline A |
| description | Matrix metalloproteinase-8 (MMP-8) promotes lung fibrotic responses to bleomycin in mice. Although prior studies reported that MMP-8 levels are increased in plasma and bronchoalveolar lavage fluid (BALF) samples from IPF patients, neither the bioactive forms nor the cellular sources of MMP-8 in idiopathic pulmonary fibrosis (IPF) patients have been identified. It is not known whether MMP-8 expression is dys-regulated in IPF leukocytes or whether MMP-8 plasma levels correlate with IPF outcomes. Our goal was to address these knowledge gaps.
We measured MMP-8 levels and forms in blood and lung samples from IPF patients versus controls using ELISAs, western blotting, and qPCR, and assessed whether MMP-8 plasma levels in 73 IPF patients correlate with rate of lung function decline and mortality. We used immunostaining to localize MMP-8 expression in IPF lungs. We quantified MMP-8 levels and forms in blood leukocytes from IPF patients versus controls.
IPF patients have increased BALF, whole lung, and plasma levels of soluble MMP-8 protein. Active MMP-8 is the main form elevated in IPF lungs. MMP-8 mRNA levels are increased in monocytes from IPF patients, but IPF patients and controls have similar levels of MMP-8 in PMNs. Surprisingly, macrophages and airway epithelial cells are the main cells expressing MMP-8 in IPF lungs. Plasma and BALF MMP-8 levels do not correlate with decline in lung function and/or mortality in IPF patients.
Blood and lung MMP-8 levels are increased in IPF patients. Active MMP-8 is the main form elevated in IPF lungs. Surprisingly, blood monocytes, lung macrophages, and airway epithelial cells are the main cells in which MMP-8 is upregulated in IPF patients. Plasma and BALF MMP-8 levels are unlikely to serve as a prognostic biomarker for IPF patients. These results provide new information about the expression patterns of MMP-8 in IPF patients. |
| doi_str_mv | 10.1371/journal.pone.0097485 |
| format | Article |
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We measured MMP-8 levels and forms in blood and lung samples from IPF patients versus controls using ELISAs, western blotting, and qPCR, and assessed whether MMP-8 plasma levels in 73 IPF patients correlate with rate of lung function decline and mortality. We used immunostaining to localize MMP-8 expression in IPF lungs. We quantified MMP-8 levels and forms in blood leukocytes from IPF patients versus controls.
IPF patients have increased BALF, whole lung, and plasma levels of soluble MMP-8 protein. Active MMP-8 is the main form elevated in IPF lungs. MMP-8 mRNA levels are increased in monocytes from IPF patients, but IPF patients and controls have similar levels of MMP-8 in PMNs. Surprisingly, macrophages and airway epithelial cells are the main cells expressing MMP-8 in IPF lungs. Plasma and BALF MMP-8 levels do not correlate with decline in lung function and/or mortality in IPF patients.
Blood and lung MMP-8 levels are increased in IPF patients. Active MMP-8 is the main form elevated in IPF lungs. Surprisingly, blood monocytes, lung macrophages, and airway epithelial cells are the main cells in which MMP-8 is upregulated in IPF patients. Plasma and BALF MMP-8 levels are unlikely to serve as a prognostic biomarker for IPF patients. These results provide new information about the expression patterns of MMP-8 in IPF patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0097485</identifier><identifier>PMID: 24828408</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Alveoli ; Biology and Life Sciences ; Biomarkers ; Bleomycin ; Blood ; Bronchoalveolar Lavage Fluid - chemistry ; Bronchus ; Cardiovascular disease ; Chronic obstructive pulmonary disease ; Collagen ; Correlation ; Critical care ; Epithelial cells ; Epithelial Cells - metabolism ; Female ; Fibroblasts ; Fibrosis ; Gene expression ; Hepatitis ; Hospitals ; Humans ; Idiopathic Pulmonary Fibrosis - metabolism ; Leukocytes ; Leukocytes (mononuclear) ; Leukocytes - metabolism ; Lung - metabolism ; Lung diseases ; Lungs ; Macrophages ; Macrophages, Alveolar - metabolism ; Male ; Matrix metalloproteinase ; Matrix Metalloproteinase 8 - blood ; Matrix Metalloproteinase 8 - metabolism ; Measurement methods ; Medical schools ; Medicine ; Medicine and Health Sciences ; Metalloproteinase ; Middle Aged ; Monocytes ; Mononuclear Phagocyte System - metabolism ; Mortality ; mRNA ; Neutrophil collagenase ; Neutrophils ; Patients ; Phagocytes ; Plasma ; Plasma levels ; Pulmonary fibrosis ; Respiratory function ; Respiratory tract ; Respiratory tract diseases ; RNA ; Rodents ; Studies ; Western blotting ; Womens health</subject><ispartof>PloS one, 2014-05, Vol.9 (5), p.e97485-e97485</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Craig et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Craig et al 2014 Craig et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-ab4805ac7592b6a74a5bff165558eb6f652daee94db077e2936a869ecc448b333</citedby><cites>FETCH-LOGICAL-c593t-ab4805ac7592b6a74a5bff165558eb6f652daee94db077e2936a869ecc448b333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020836/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020836/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,2098,2917,23849,27907,27908,53774,53776,79351,79352</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24828408$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mora, Ana</contributor><creatorcontrib>Craig, Vanessa J</creatorcontrib><creatorcontrib>Polverino, Francesca</creatorcontrib><creatorcontrib>Laucho-Contreras, Maria E</creatorcontrib><creatorcontrib>Shi, Yuanyuan</creatorcontrib><creatorcontrib>Liu, Yushi</creatorcontrib><creatorcontrib>Osorio, Juan C</creatorcontrib><creatorcontrib>Tesfaigzi, Yohannes</creatorcontrib><creatorcontrib>Pinto-Plata, Victor</creatorcontrib><creatorcontrib>Gochuico, Bernadette R</creatorcontrib><creatorcontrib>Rosas, Ivan O</creatorcontrib><creatorcontrib>Owen, Caroline A</creatorcontrib><title>Mononuclear phagocytes and airway epithelial cells: novel sources of matrix metalloproteinase-8 (MMP-8) in patients with idiopathic pulmonary fibrosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Matrix metalloproteinase-8 (MMP-8) promotes lung fibrotic responses to bleomycin in mice. Although prior studies reported that MMP-8 levels are increased in plasma and bronchoalveolar lavage fluid (BALF) samples from IPF patients, neither the bioactive forms nor the cellular sources of MMP-8 in idiopathic pulmonary fibrosis (IPF) patients have been identified. It is not known whether MMP-8 expression is dys-regulated in IPF leukocytes or whether MMP-8 plasma levels correlate with IPF outcomes. Our goal was to address these knowledge gaps.
We measured MMP-8 levels and forms in blood and lung samples from IPF patients versus controls using ELISAs, western blotting, and qPCR, and assessed whether MMP-8 plasma levels in 73 IPF patients correlate with rate of lung function decline and mortality. We used immunostaining to localize MMP-8 expression in IPF lungs. We quantified MMP-8 levels and forms in blood leukocytes from IPF patients versus controls.
IPF patients have increased BALF, whole lung, and plasma levels of soluble MMP-8 protein. Active MMP-8 is the main form elevated in IPF lungs. MMP-8 mRNA levels are increased in monocytes from IPF patients, but IPF patients and controls have similar levels of MMP-8 in PMNs. Surprisingly, macrophages and airway epithelial cells are the main cells expressing MMP-8 in IPF lungs. Plasma and BALF MMP-8 levels do not correlate with decline in lung function and/or mortality in IPF patients.
Blood and lung MMP-8 levels are increased in IPF patients. Active MMP-8 is the main form elevated in IPF lungs. Surprisingly, blood monocytes, lung macrophages, and airway epithelial cells are the main cells in which MMP-8 is upregulated in IPF patients. Plasma and BALF MMP-8 levels are unlikely to serve as a prognostic biomarker for IPF patients. These results provide new information about the expression patterns of MMP-8 in IPF patients.</description><subject>Aged</subject><subject>Alveoli</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Bleomycin</subject><subject>Blood</subject><subject>Bronchoalveolar Lavage Fluid - chemistry</subject><subject>Bronchus</subject><subject>Cardiovascular disease</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Collagen</subject><subject>Correlation</subject><subject>Critical care</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - metabolism</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Hepatitis</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Idiopathic Pulmonary Fibrosis - metabolism</subject><subject>Leukocytes</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes - metabolism</subject><subject>Lung - metabolism</subject><subject>Lung diseases</subject><subject>Lungs</subject><subject>Macrophages</subject><subject>Macrophages, Alveolar - metabolism</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 8 - blood</subject><subject>Matrix Metalloproteinase 8 - metabolism</subject><subject>Measurement methods</subject><subject>Medical schools</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metalloproteinase</subject><subject>Middle Aged</subject><subject>Monocytes</subject><subject>Mononuclear Phagocyte System - metabolism</subject><subject>Mortality</subject><subject>mRNA</subject><subject>Neutrophil collagenase</subject><subject>Neutrophils</subject><subject>Patients</subject><subject>Phagocytes</subject><subject>Plasma</subject><subject>Plasma levels</subject><subject>Pulmonary fibrosis</subject><subject>Respiratory function</subject><subject>Respiratory tract</subject><subject>Respiratory tract diseases</subject><subject>RNA</subject><subject>Rodents</subject><subject>Studies</subject><subject>Western blotting</subject><subject>Womens 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phagocytes and airway epithelial cells: novel sources of matrix metalloproteinase-8 (MMP-8) in patients with idiopathic pulmonary fibrosis</title><author>Craig, Vanessa J ; Polverino, Francesca ; Laucho-Contreras, Maria E ; Shi, Yuanyuan ; Liu, Yushi ; Osorio, Juan C ; Tesfaigzi, Yohannes ; Pinto-Plata, Victor ; Gochuico, Bernadette R ; Rosas, Ivan O ; Owen, Caroline A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-ab4805ac7592b6a74a5bff165558eb6f652daee94db077e2936a869ecc448b333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aged</topic><topic>Alveoli</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Bleomycin</topic><topic>Blood</topic><topic>Bronchoalveolar Lavage Fluid - chemistry</topic><topic>Bronchus</topic><topic>Cardiovascular disease</topic><topic>Chronic obstructive pulmonary 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Francesca</au><au>Laucho-Contreras, Maria E</au><au>Shi, Yuanyuan</au><au>Liu, Yushi</au><au>Osorio, Juan C</au><au>Tesfaigzi, Yohannes</au><au>Pinto-Plata, Victor</au><au>Gochuico, Bernadette R</au><au>Rosas, Ivan O</au><au>Owen, Caroline A</au><au>Mora, Ana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mononuclear phagocytes and airway epithelial cells: novel sources of matrix metalloproteinase-8 (MMP-8) in patients with idiopathic pulmonary fibrosis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-05-14</date><risdate>2014</risdate><volume>9</volume><issue>5</issue><spage>e97485</spage><epage>e97485</epage><pages>e97485-e97485</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Matrix metalloproteinase-8 (MMP-8) promotes lung fibrotic responses to bleomycin in mice. Although prior studies reported that MMP-8 levels are increased in plasma and bronchoalveolar lavage fluid (BALF) samples from IPF patients, neither the bioactive forms nor the cellular sources of MMP-8 in idiopathic pulmonary fibrosis (IPF) patients have been identified. It is not known whether MMP-8 expression is dys-regulated in IPF leukocytes or whether MMP-8 plasma levels correlate with IPF outcomes. Our goal was to address these knowledge gaps.
We measured MMP-8 levels and forms in blood and lung samples from IPF patients versus controls using ELISAs, western blotting, and qPCR, and assessed whether MMP-8 plasma levels in 73 IPF patients correlate with rate of lung function decline and mortality. We used immunostaining to localize MMP-8 expression in IPF lungs. We quantified MMP-8 levels and forms in blood leukocytes from IPF patients versus controls.
IPF patients have increased BALF, whole lung, and plasma levels of soluble MMP-8 protein. Active MMP-8 is the main form elevated in IPF lungs. MMP-8 mRNA levels are increased in monocytes from IPF patients, but IPF patients and controls have similar levels of MMP-8 in PMNs. Surprisingly, macrophages and airway epithelial cells are the main cells expressing MMP-8 in IPF lungs. Plasma and BALF MMP-8 levels do not correlate with decline in lung function and/or mortality in IPF patients.
Blood and lung MMP-8 levels are increased in IPF patients. Active MMP-8 is the main form elevated in IPF lungs. Surprisingly, blood monocytes, lung macrophages, and airway epithelial cells are the main cells in which MMP-8 is upregulated in IPF patients. Plasma and BALF MMP-8 levels are unlikely to serve as a prognostic biomarker for IPF patients. These results provide new information about the expression patterns of MMP-8 in IPF patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24828408</pmid><doi>10.1371/journal.pone.0097485</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-05, Vol.9 (5), p.e97485-e97485 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1524628325 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aged Alveoli Biology and Life Sciences Biomarkers Bleomycin Blood Bronchoalveolar Lavage Fluid - chemistry Bronchus Cardiovascular disease Chronic obstructive pulmonary disease Collagen Correlation Critical care Epithelial cells Epithelial Cells - metabolism Female Fibroblasts Fibrosis Gene expression Hepatitis Hospitals Humans Idiopathic Pulmonary Fibrosis - metabolism Leukocytes Leukocytes (mononuclear) Leukocytes - metabolism Lung - metabolism Lung diseases Lungs Macrophages Macrophages, Alveolar - metabolism Male Matrix metalloproteinase Matrix Metalloproteinase 8 - blood Matrix Metalloproteinase 8 - metabolism Measurement methods Medical schools Medicine Medicine and Health Sciences Metalloproteinase Middle Aged Monocytes Mononuclear Phagocyte System - metabolism Mortality mRNA Neutrophil collagenase Neutrophils Patients Phagocytes Plasma Plasma levels Pulmonary fibrosis Respiratory function Respiratory tract Respiratory tract diseases RNA Rodents Studies Western blotting Womens health |
| title | Mononuclear phagocytes and airway epithelial cells: novel sources of matrix metalloproteinase-8 (MMP-8) in patients with idiopathic pulmonary fibrosis |
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