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10.1164/rccm.201401-0145OC http://scihub22266oqcxt.onion/10.1164/rccm.201401-0145OC C4226028!4226028!24874071     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Am+J+Respir+Crit+Care+Med 2014 ; 190 (1): 51-61 Nephropedia Template TP {{tp|p=24874071|t=2014. An Aberrant Leukotriene A4 Hydrolase?Proline-Glycine-Proline Pathway in the Pathogenesis of Chronic Obstructive Pulmonary Disease |pdf=|usr=}}{{24874071}} gab.com Text An Aberrant Leukotriene A4 Hydrolase Proline-Glycine-Proline Pathway in the Pathogenesis of Chronic Obstructive Pulmonary Disease JO: Am J Respir Crit Care Med http://www.kidney.de/pget.php?&tw=1&pmid=24874071 #FOAvip Rationale: Chronic neutrophilic inflammation is a hallmark in the pathogenesis of chronic obstructive pulmonary disease (COPD) and persists after cigarette smoking has stopped. Mechanisms involved in this ongoing inflammatory response have not been delineated.Objectives: We investigated changes to the leukotriene A4 hydrolase (LTA4H)?proline-glycine-proline (PGP) pathway and chronic inflammation in the development of COPD.Methods: A/J mice were exposed to air or cigarette smoke for 22 weeks followed by bronchoalveolar lavage and lung and cardiac tissue analysis. Two human cohorts were used to analyze changes to the LTA4H?PGP pathway in never smokers, control smokers, COPD smokers, and COPD former smokers. PGP/AcPGP and LTA4H aminopeptidase activity were detected by mass spectroscopy, LTA4H amounts were detected by ELISA, and acrolein was detected by Western blot.Measurements and Main Results: Mice exposed to cigarette smoke developed emphysema with increased PGP, neutrophilic inflammation, and selective inhibition of LTA4H aminopeptidase, which ordinarily degrades PGP. We recapitulated these findings in smokers with and without COPD. PGP and AcPGP are closely associated with cigarette smoke use. Once chronic inflammation is established, changes to LTA4H aminopeptidase remain, even in the absence of ongoing cigarette use. Acrolein modifies LTA4H and inhibits aminopeptidase activity to the same extent as cigarette smoke.Conclusions: These results demonstrate a novel pathway of aberrant regulation of PGP/AcPGP, suggesting this inflammatory pathway may be intimately involved in disease progression in the absence of ongoing cigarette smoke exposure. We highlight a mechanism by which acrolein potentiates neutrophilic inflammation through selective inhibition of LTA4H aminopeptidase activity.Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). Twit Text FOAVip An Aberrant Leukotriene A4 Hydrolase Proline-Glycine-Proline Pathway in the Pathogenesis of Chronic Obstructive Pulmonary Disease ????Am J Respir Crit Care Med http://www.kidney.de/pget.php?&tw=1&pmid=24874071 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24874071 #FOAvip English Wikipedia <ref>{{Cite pmid|24874071}}</ref> An Aberrant Leukotriene A4 Hydrolase?Proline-Glycine-Proline Pathway in the Pathogenesis of Chronic Obstructive Pulmonary Disease #MMPMID24874071 Wells JM; O?Reilly PJ; Szul T; Sullivan DI; Handley G; Garrett C; McNicholas CM; Roda MA; Miller BE; Tal-Singer R; Gaggar A; Rennard SI; Jackson PL; Blalock JE Am J Respir Crit Care Med 2014[Jul]; 190 (1): 51-61 PMID24874071show ga Rationale: Chronic neutrophilic inflammation is a hallmark in the pathogenesis of chronic obstructive pulmonary disease (COPD) and persists after cigarette smoking has stopped. Mechanisms involved in this ongoing inflammatory response have not been delineated.Objectives: We investigated changes to the leukotriene A4 hydrolase (LTA4H)?proline-glycine-proline (PGP) pathway and chronic inflammation in the development of COPD.Methods: A/J mice were exposed to air or cigarette smoke for 22 weeks followed by bronchoalveolar lavage and lung and cardiac tissue analysis. Two human cohorts were used to analyze changes to the LTA4H?PGP pathway in never smokers, control smokers, COPD smokers, and COPD former smokers. PGP/AcPGP and LTA4H aminopeptidase activity were detected by mass spectroscopy, LTA4H amounts were detected by ELISA, and acrolein was detected by Western blot.Measurements and Main Results: Mice exposed to cigarette smoke developed emphysema with increased PGP, neutrophilic inflammation, and selective inhibition of LTA4H aminopeptidase, which ordinarily degrades PGP. We recapitulated these findings in smokers with and without COPD. PGP and AcPGP are closely associated with cigarette smoke use. Once chronic inflammation is established, changes to LTA4H aminopeptidase remain, even in the absence of ongoing cigarette use. Acrolein modifies LTA4H and inhibits aminopeptidase activity to the same extent as cigarette smoke.Conclusions: These results demonstrate a novel pathway of aberrant regulation of PGP/AcPGP, suggesting this inflammatory pathway may be intimately involved in disease progression in the absence of ongoing cigarette smoke exposure. We highlight a mechanism by which acrolein potentiates neutrophilic inflammation through selective inhibition of LTA4H aminopeptidase activity.Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). äAn Aberrant Leukotriene A4 Hydrolase?Proline-Glycine-Proline Pathway i(epmc).pdf DeepDyve Pubget Overpricing