大葉大學圖書館 |

The functional significance of the lung-liver axis during pneumonia.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
書名/作者:	The functional significance of the lung-liver axis during pneumonia.
作者:	Hilliard, Kristie Lee.
面頁冊數:	210 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-03(E), Section: B.
Contained By:	Dissertation Abstracts International77-03B(E).
標題:	Immunology.
標題:	Microbiology.
ISBN:	9781339219929
摘要、提要註:	The hepatic acute phase response (APR), stimulated by injury or inflammation, is characterized by significant changes in circulating acute phase protein (APP) concentrations. While individual functions of liver-derived APPs are known, the net consequence of APP changes is unclear. Pneumonia and sepsis elicit systemic inflammation and induce a robust APR. Although APR activation is regarded as a hallmark of infection, direct contributions of liver activation to pulmonary defense during pneumonia and sepsis-induced pneumonia remain unclear. Pneumonia causes a pulmonary inflammatory response coordinated largely by alveolar macrophages, and is typified by cytokine production, leukocyte recruitment and plasma extravasation, the latter of can enable delivery of hepatocyte-derived APPs to the infection site. To determine the functional significance of the hepatic APR during pneumonia, we challenged APR-null mice lacking hepatocyte signal transducer and activator of transcription-3 (STAT3) and RelA with 106 colony-forming units (CFU) Escherichia coli intratracheally. HepSTAT3/RelA-/- mice displayed ablated APP induction, significantly increased mortality, tumor necrosis factor-dependent hepatotoxicity, and pulmonary bacterial burdens. Following a lower (4x10 5 CFU) E. coli inoculum, hepSTAT3/RelA-/- mice had decreased APP concentrations with reduced pulmonary inflammation and diminished airspace macrophage activation. Similar results were obtained in the context of endotoxemia and pneumonia. We employed an endotoxemia/pneumonia model, whereby 18 hours of intraperitoneal E. coli lipopolysaccharide (5 mg/kg) was followed by intratracheal E. coli (10 6 CFU) in mice lacking hepatocyte STAT3 (hepSTAT3-/-) or control hepSTAT3+/+ mice. Following endotoxemia and pneumonia, hepSTAT3-/- mice, with significantly reduced levels of circulating and airspace APPs, exhibited significantly elevated lung and blood bacterial burdens and mortality. While neither recruited airspace neutrophils nor lung injury were altered in endotoxemic hepSTAT3-/- mice, in vivo production of reactive oxygen species in alveolar macrophage was significantly decreased. Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3-/- mice allowed greater bacterial growth ex vivo. These results identify a lung-liver axis, whereby the liver response enhances macrophage activation and pulmonary host defense during pneumonia and sepsis-induced pneumonia. Taken together, induction of liver acute phase gene expression programs contributes to countering the deleterious consequences of pneumonia, whether it is alone or in the context of sepsis-induced infection.
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3733676

The functional significance of the lung-liver axis during pneumonia.
Hilliard, Kristie Lee.

The functional significance of the lung-liver axis during pneumonia. - 210 p.

Source: Dissertation Abstracts International, Volume: 77-03(E), Section: B.

Thesis (Ph.D.)--Boston University, 2015.

The hepatic acute phase response (APR), stimulated by injury or inflammation, is characterized by significant changes in circulating acute phase protein (APP) concentrations. While individual functions of liver-derived APPs are known, the net consequence of APP changes is unclear. Pneumonia and sepsis elicit systemic inflammation and induce a robust APR. Although APR activation is regarded as a hallmark of infection, direct contributions of liver activation to pulmonary defense during pneumonia and sepsis-induced pneumonia remain unclear. Pneumonia causes a pulmonary inflammatory response coordinated largely by alveolar macrophages, and is typified by cytokine production, leukocyte recruitment and plasma extravasation, the latter of can enable delivery of hepatocyte-derived APPs to the infection site. To determine the functional significance of the hepatic APR during pneumonia, we challenged APR-null mice lacking hepatocyte signal transducer and activator of transcription-3 (STAT3) and RelA with 106 colony-forming units (CFU) Escherichia coli intratracheally. HepSTAT3/RelA-/- mice displayed ablated APP induction, significantly increased mortality, tumor necrosis factor-dependent hepatotoxicity, and pulmonary bacterial burdens. Following a lower (4x10 5 CFU) E. coli inoculum, hepSTAT3/RelA-/- mice had decreased APP concentrations with reduced pulmonary inflammation and diminished airspace macrophage activation. Similar results were obtained in the context of endotoxemia and pneumonia. We employed an endotoxemia/pneumonia model, whereby 18 hours of intraperitoneal E. coli lipopolysaccharide (5 mg/kg) was followed by intratracheal E. coli (10 6 CFU) in mice lacking hepatocyte STAT3 (hepSTAT3-/-) or control hepSTAT3+/+ mice. Following endotoxemia and pneumonia, hepSTAT3-/- mice, with significantly reduced levels of circulating and airspace APPs, exhibited significantly elevated lung and blood bacterial burdens and mortality. While neither recruited airspace neutrophils nor lung injury were altered in endotoxemic hepSTAT3-/- mice, in vivo production of reactive oxygen species in alveolar macrophage was significantly decreased. Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3-/- mice allowed greater bacterial growth ex vivo. These results identify a lung-liver axis, whereby the liver response enhances macrophage activation and pulmonary host defense during pneumonia and sepsis-induced pneumonia. Taken together, induction of liver acute phase gene expression programs contributes to countering the deleterious consequences of pneumonia, whether it is alone or in the context of sepsis-induced infection.

ISBN: 9781339219929Subjects--Topical Terms:

402223
Immunology.

The functional significance of the lung-liver axis during pneumonia.
LDR:03533nam a2200277 4500 001 441016
005 20160422125048.5
008 160525s2015 ||||||||||||||||| ||eng d
020 $a 9781339219929
035 $a (MiAaPQ)AAI3733676
035 $a AAI3733676
040 $a MiAaPQ $c MiAaPQ
100 1 $a Hilliard, Kristie Lee. $3 630094
245 1 4 $a The functional significance of the lung-liver axis during pneumonia.
300 $a 210 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-03(E), Section: B.
500 $a Adviser: Lee J. Quinton.
502 $a Thesis (Ph.D.)--Boston University, 2015.
520 $a The hepatic acute phase response (APR), stimulated by injury or inflammation, is characterized by significant changes in circulating acute phase protein (APP) concentrations. While individual functions of liver-derived APPs are known, the net consequence of APP changes is unclear. Pneumonia and sepsis elicit systemic inflammation and induce a robust APR. Although APR activation is regarded as a hallmark of infection, direct contributions of liver activation to pulmonary defense during pneumonia and sepsis-induced pneumonia remain unclear. Pneumonia causes a pulmonary inflammatory response coordinated largely by alveolar macrophages, and is typified by cytokine production, leukocyte recruitment and plasma extravasation, the latter of can enable delivery of hepatocyte-derived APPs to the infection site. To determine the functional significance of the hepatic APR during pneumonia, we challenged APR-null mice lacking hepatocyte signal transducer and activator of transcription-3 (STAT3) and RelA with 106 colony-forming units (CFU) Escherichia coli intratracheally. HepSTAT3/RelA-/- mice displayed ablated APP induction, significantly increased mortality, tumor necrosis factor-dependent hepatotoxicity, and pulmonary bacterial burdens. Following a lower (4x10 5 CFU) E. coli inoculum, hepSTAT3/RelA-/- mice had decreased APP concentrations with reduced pulmonary inflammation and diminished airspace macrophage activation. Similar results were obtained in the context of endotoxemia and pneumonia. We employed an endotoxemia/pneumonia model, whereby 18 hours of intraperitoneal E. coli lipopolysaccharide (5 mg/kg) was followed by intratracheal E. coli (10 6 CFU) in mice lacking hepatocyte STAT3 (hepSTAT3-/-) or control hepSTAT3+/+ mice. Following endotoxemia and pneumonia, hepSTAT3-/- mice, with significantly reduced levels of circulating and airspace APPs, exhibited significantly elevated lung and blood bacterial burdens and mortality. While neither recruited airspace neutrophils nor lung injury were altered in endotoxemic hepSTAT3-/- mice, in vivo production of reactive oxygen species in alveolar macrophage was significantly decreased. Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3-/- mice allowed greater bacterial growth ex vivo. These results identify a lung-liver axis, whereby the liver response enhances macrophage activation and pulmonary host defense during pneumonia and sepsis-induced pneumonia. Taken together, induction of liver acute phase gene expression programs contributes to countering the deleterious consequences of pneumonia, whether it is alone or in the context of sepsis-induced infection.
590 $a School code: 0017.
650 4 $a Immunology. $3 402223
650 4 $a Microbiology. $3 182563
690 $a 0982
690 $a 0410
710 2 $a Boston University. $b Microbiology GMS. $3 630095
773 0 $t Dissertation Abstracts International $g 77-03B(E).
790 $a 0017
791 $a Ph.D.
792 $a 2015
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3733676