東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

The role of SHIP in macrophage diffe...

Rauh, Michael J.

FindBook

Google Book

Amazon

博客來

The role of SHIP in macrophage differentiation and function.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The role of SHIP in macrophage differentiation and function./
作者:	Rauh, Michael J.
面頁冊數:	173 p.
附註:	Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2238.
Contained By:	Dissertation Abstracts International68-04B.
標題:	Health Sciences, Immunology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR26778
ISBN:	9780494267783

The role of SHIP in macrophage differentiation and function.
Rauh, Michael J.

The role of SHIP in macrophage differentiation and function. - 173 p.

Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2238.

Thesis (M.D.)--The University of British Columbia (Canada), 2007.

The SH2 containing inositol 5'-phosphatase (SHIP) is a hemopoietic-specific protein that catalyzes the hydrolysis of the phosphatidylinositol 3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3), to PI-3,4-P2 (PIP2) and thereby negatively regulates hemopoietic cell survival, proliferation, differentiation and activation. Herein, macrophage development and function were compared in SHIP+/+ and -/- mice. SHIP was found to restrain in vitro bone marrow-derived macrophage (BMMphi) survival (or proliferation) and differentiation, consistent with the increased number of macrophages observed in SHIP-/- mice. We also compared the function of J2 virus-transformed SHIP+/+ and -/- BMMphi cell lines and found that SHIP-/- J2M BMMphi cell lines (-/-J2Ms) were functionally impaired in inducible nitric oxide (NO) synthase (iNOS) induction and high-output NO production, an important, classical (M1) macrophage activation strategy to combat the growth of tumours and microorganisms. This was ascribed to deficient nuclear localization of IRF1 and inhibition of iNOS transcription in these transformed macrophages. In contrast, primary SHIP-/- BMMphis routinely demonstrated enhanced LPS-stimulated iNOS/NO induction, likely as a result of PI3K-mediated enhancement of the p70S6K/IFNbeta/Stat1/iNOS pathway. Differential impacts upon this axis also provided an explanation for the opposite effects of the PI3K inhibitors, LY294002 and wortmannin, on iNOS/NO. We also found that SHIP-/- BMMphis failed to tolerize to a second dose of LPS, likely because SHIP protein levels were upregulated in wild-type BMMphis in an autocrine-acting, TGFP-mediated tolerance loop.

ISBN: 9780494267783Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

The role of SHIP in macrophage differentiation and function.
LDR:03479nmm 2200253 4500 001 1835890
005 20080107105544.5
008 130610s2007 eng d
020 $a 9780494267783
035 $a (UMI)AAINR26778
035 $a AAINR26778
040 $a UMI $c UMI
100 1 $a Rauh, Michael J. $3 1924510
245 1 4 $a The role of SHIP in macrophage differentiation and function.
300 $a 173 p.
500 $a Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2238.
502 $a Thesis (M.D.)--The University of British Columbia (Canada), 2007.
520 $a The SH2 containing inositol 5'-phosphatase (SHIP) is a hemopoietic-specific protein that catalyzes the hydrolysis of the phosphatidylinositol 3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3), to PI-3,4-P2 (PIP2) and thereby negatively regulates hemopoietic cell survival, proliferation, differentiation and activation. Herein, macrophage development and function were compared in SHIP+/+ and -/- mice. SHIP was found to restrain in vitro bone marrow-derived macrophage (BMMphi) survival (or proliferation) and differentiation, consistent with the increased number of macrophages observed in SHIP-/- mice. We also compared the function of J2 virus-transformed SHIP+/+ and -/- BMMphi cell lines and found that SHIP-/- J2M BMMphi cell lines (-/-J2Ms) were functionally impaired in inducible nitric oxide (NO) synthase (iNOS) induction and high-output NO production, an important, classical (M1) macrophage activation strategy to combat the growth of tumours and microorganisms. This was ascribed to deficient nuclear localization of IRF1 and inhibition of iNOS transcription in these transformed macrophages. In contrast, primary SHIP-/- BMMphis routinely demonstrated enhanced LPS-stimulated iNOS/NO induction, likely as a result of PI3K-mediated enhancement of the p70S6K/IFNbeta/Stat1/iNOS pathway. Differential impacts upon this axis also provided an explanation for the opposite effects of the PI3K inhibitors, LY294002 and wortmannin, on iNOS/NO. We also found that SHIP-/- BMMphis failed to tolerize to a second dose of LPS, likely because SHIP protein levels were upregulated in wild-type BMMphis in an autocrine-acting, TGFP-mediated tolerance loop.
520 $a Analysis of in vivo-differentiated, resident peritoneal and alveolar macrophages (PMphis, AMphis) from SHIP-/- mice revealed impaired NO generation, despite sufficient iNOS induction, due to constitutive arginase I-mediated L-arginine substrate competition, which redirected L-arginine metabolism away from cytotoxic NO and towards the production of healing/inflammation-resolving intermediates. These and other features were recognized as alternative (M2) macrophage activation. Consistent with pathological M2-skewing in SHIP-/- mice, their lungs were fibrotic and contained macrophage-associated Ym1 crystals. Moreover, implanted tumours grew more rapidly in the M2-skewed environment of SHIP-/- mice. Interestingly, BMMphis from SHIP-/- mice did not display this M2 phenotype unless exposed to TGFbeta-containing mouse plasma early during in vitro differentiation, suggesting that an environment of elevated PIP3 and TGFbeta arising during in vivo macrophage differentiation may contribute to M2-skewing.
590 $a School code: 2500.
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0982
710 2 $a The University of British Columbia (Canada). $3 626643
773 0 $t Dissertation Abstracts International $g 68-04B.
790 $a 2500
791 $a M.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR26778