Home
|
Inbox
|
Search
|
View Abstract
Distribution of Ac-PGP in Mice After Intratracheal Administration
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A4759 - Distribution of Ac-PGP in Mice After Intratracheal Administration
Author Block: X. Xu1, J. Li1, L. Viera1, N. Yi2, J. E. Blalock1, A. Gaggar1; 1Medicine, UAB, Birmingham, AL, United States, 2Biostatistics, UAB, Birmingham, AL, United States.
Introduction: Proline-glycine-proline (PGP), a neutrophil chemoattractant in chronic inflammation generated from the breakdown of collagen, is involved in the development of emphysema-like changes in the airways and right ventricular hypertrophy. The purpose of this study is to examine tissue distribution with acetylated PGP (Ac-PGP) following intratracheal administration in mice and determine whether Ac-PGP induces endogenous PGP/Ac-PGP generation.
Methods: C56BL/6j female mice were intratracheally (IT) instilled with a single C13 N15 Ac-PGP (labeled Ac-PGP) dose (250 µg). At multiple time points (1, 4, 8, 24, 48 hours), these animals (n=3-5 per time point) had bronchoalveolar lavage (BAL), serum, pulmonary artery window (PW), lung, heart, liver, brain, spleen, thymus and kidney collected for the systemic distribution of the labeled peptide and endogenous PGP/Ac-PGP by using electron spray ionization tandem mass spectrometry (ESI-LC-MS/MS).
Results: In the animals given labeled Ac-PGP IT, a significant quantity of Ac-PGP was found of the BAL and serum. These results demonstrate the potential of translocation of Ac-PGP from the airways into the systemic compartment of these animals. To more specifically assess this effect, we tracked the distribution of labeled Ac-PGP after IT administration. At multiple time points after a single dose of a labeled Ac-PGP, most organ had a detectable level of labeled Ac-PGP at 8h but the lung was detectable at 24 hours. In addition, endogenous Ac-PGP was found in the lung and vascular bed at 1h and 4h post labeled Ac-PGP administration.
Conclusion: These results demonstrate that Ac-PGP IT enter the systemic circulation, thereby highlighting the potential for the peptides to act directly on the endothelium in vivo. The generation of endogenous PGP/Ac-PGP suggest that these peptides may serve as an important switch to a self-propagating inflammatory state in a myriad of disorders.
Grant support: These studies were funded in part by grants from the AHA (16SDG27040000 to XX), NIH (HL07783, HL090999 and HL087824 to JEB; HL102371 29 to AG; HL126596 to JEB and AG), Cystic Fibrosis Foundation Therapeutics 30 (GAGGARA0 to AG), the Veterans Administration (1 I01 BX001756 to AG), and the 31 Ismail Moustapha Scholar Fund (to AG).
Author Block: X. Xu1, J. Li1, L. Viera1, N. Yi2, J. E. Blalock1, A. Gaggar1; 1Medicine, UAB, Birmingham, AL, United States, 2Biostatistics, UAB, Birmingham, AL, United States.
Introduction: Proline-glycine-proline (PGP), a neutrophil chemoattractant in chronic inflammation generated from the breakdown of collagen, is involved in the development of emphysema-like changes in the airways and right ventricular hypertrophy. The purpose of this study is to examine tissue distribution with acetylated PGP (Ac-PGP) following intratracheal administration in mice and determine whether Ac-PGP induces endogenous PGP/Ac-PGP generation.
Methods: C56BL/6j female mice were intratracheally (IT) instilled with a single C13 N15 Ac-PGP (labeled Ac-PGP) dose (250 µg). At multiple time points (1, 4, 8, 24, 48 hours), these animals (n=3-5 per time point) had bronchoalveolar lavage (BAL), serum, pulmonary artery window (PW), lung, heart, liver, brain, spleen, thymus and kidney collected for the systemic distribution of the labeled peptide and endogenous PGP/Ac-PGP by using electron spray ionization tandem mass spectrometry (ESI-LC-MS/MS).
Results: In the animals given labeled Ac-PGP IT, a significant quantity of Ac-PGP was found of the BAL and serum. These results demonstrate the potential of translocation of Ac-PGP from the airways into the systemic compartment of these animals. To more specifically assess this effect, we tracked the distribution of labeled Ac-PGP after IT administration. At multiple time points after a single dose of a labeled Ac-PGP, most organ had a detectable level of labeled Ac-PGP at 8h but the lung was detectable at 24 hours. In addition, endogenous Ac-PGP was found in the lung and vascular bed at 1h and 4h post labeled Ac-PGP administration.
Conclusion: These results demonstrate that Ac-PGP IT enter the systemic circulation, thereby highlighting the potential for the peptides to act directly on the endothelium in vivo. The generation of endogenous PGP/Ac-PGP suggest that these peptides may serve as an important switch to a self-propagating inflammatory state in a myriad of disorders.
Grant support: These studies were funded in part by grants from the AHA (16SDG27040000 to XX), NIH (HL07783, HL090999 and HL087824 to JEB; HL102371 29 to AG; HL126596 to JEB and AG), Cystic Fibrosis Foundation Therapeutics 30 (GAGGARA0 to AG), the Veterans Administration (1 I01 BX001756 to AG), and the 31 Ismail Moustapha Scholar Fund (to AG).
|
Home
|
Inbox
|
Search
|