Hemoglobin induced cell trauma indirectly influences endothelial TLR9 activity resulting in pulmonary vascular smooth muscle cell activation
Publication Date
February 02, 2017
Authors
Zoe Loomis, Paul Eigenberger, Katherine Redinius, Christina Lisk, et al
Volume
12
Issue
2
Pages
e0171219
DOI
https://dx.plos.org/10.1371/journal.pone.0171219
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0171219
Web of Science
000396161200106
Scopus
85011324285
Mendeley
http://www.mendeley.com/research/hemoglobin-induced-cell-trauma-indirectly-influences-endothelial-tlr9-activity-resulting-pulmonary-v
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Mendeley | Further Information

{"title"=>"Hemoglobin induced cell trauma indirectly influences endothelial TLR9 activity resulting in pulmonary vascular smooth muscle cell activation", "type"=>"journal", "authors"=>[{"first_name"=>"Zoe", "last_name"=>"Loomis", "scopus_author_id"=>"16025014100"}, {"first_name"=>"Paul", "last_name"=>"Eigenberger", "scopus_author_id"=>"56415015400"}, {"first_name"=>"Katherine", "last_name"=>"Redinius", "scopus_author_id"=>"57193168604"}, {"first_name"=>"Christina", "last_name"=>"Lisk", "scopus_author_id"=>"55339448200"}, {"first_name"=>"Vijaya", "last_name"=>"Karoor", "scopus_author_id"=>"6601955621"}, {"first_name"=>"Eva", "last_name"=>"Nozik-Grayck", "scopus_author_id"=>"6603306252"}, {"first_name"=>"Scott K.", "last_name"=>"Ferguson", "scopus_author_id"=>"57193170077"}, {"first_name"=>"Kathryn", "last_name"=>"Hassell", "scopus_author_id"=>"7003294247"}, {"first_name"=>"Rachelle", "last_name"=>"Nuss", "scopus_author_id"=>"7004884139"}, {"first_name"=>"Kurt", "last_name"=>"Stenmark", "scopus_author_id"=>"7006370544"}, {"first_name"=>"Paul", "last_name"=>"Buehler", "scopus_author_id"=>"6701578649"}, {"first_name"=>"David C.", "last_name"=>"Irwin", "scopus_author_id"=>"11940920100"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"614278730", "pmid"=>"28152051", "doi"=>"10.1371/journal.pone.0171219", "issn"=>"19326203", "scopus"=>"2-s2.0-85011324285", "sgr"=>"85011324285", "isbn"=>"1111111111"}, "id"=>"79da07ef-1109-30d2-a818-09b8df93b93b", "abstract"=>"© 2017 Villalonga-Olives et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. It is now well established that both inherited and acquired forms of hemolytic disease can promote pulmonary vascular disease consequent of free hemoglobin (Hb) induced NO scavenging, elevations in reactive oxygen species and lipid peroxidation. It has recently been reported that oxidative stress can activate NFkB through a toll-like receptor 9 (TLR9) mediated pathway; further, TLR9 can be activated by either nuclear or mitochondrial DNA liberated by stress induced cellular trauma. We hypothesis that Hb induced lipid peroxidation and subsequent endothelial cell trauma is linked to TLR9 activation, resulting in IL-6 mediated pulmonary smooth muscle cell proliferation. We examined the effects of Hb on rat pulmonary artery endothelial and smooth muscle cells (rPAEC and rPASMC, respectively), and then utilized TLR9 and IL6 inhibitors, as well as the Hb and heme binding proteins (haptoglobin (Hp) and hemopexin (Hpx), respectively) to further elucidate the aforementioned mediators. Further, we explored the effects of Hb in vivo utilizing endothelial cell (EC) specific myeloid differentiation primary response gene-88 (MyD88) and TLR9 null mice. Our data show that oxidized Hb induces lipid peroxidation, cellular toxicity (5.5 ± 1.7 fold; p ≥ 0.04), increased TLR9 activation (60%; p = 0.01), and up regulated IL6 expression (1.75 ±0.3 fold; p = 0.04) in rPAEC. Rat PASMC exhibited a more proliferative state (13 ± 1%; p = 0.01) when co-cultured with Hb activated rPAEC. These effects were attenuated with the sequestration of Hb or heme by Hp and Hpx as well as with TLR9 an IL-6 inhibition. Moreover, in both EC-MyD88 and TLR9 null mice Hb-infusion resulted in less lung IL-6 expression compared to WT cohorts. These results demonstrate that Hb-induced lipid peroxidation can initiate a modest TLR9 mediated inflammatory response, subsequently generating an activated SMC phenotype.", "link"=>"http://www.mendeley.com/research/hemoglobin-induced-cell-trauma-indirectly-influences-endothelial-tlr9-activity-resulting-pulmonary-v", "reader_count"=>7, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>2, "Researcher"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>2, "Researcher"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>1, "Neuroscience"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

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