Apoptosis inhibition in P. aeruginosa-induced lung injury influences lung fluid balance

Details

Serval ID
serval:BIB_3F830CD3BE57
Type
Article: article from journal or magazin.
Collection
Publications
Title
Apoptosis inhibition in P. aeruginosa-induced lung injury influences lung fluid balance
Journal
Intensive Care Med
Author(s)
Le Berre R., Faure K., Fauvel H., Viget N. B., Ader F., Prangere T., Thomas A. M., Leroy X., Pittet J. F., Marchetti P., Guery B. P.
ISSN
0342-4642 (Print)
ISSN-L
0342-4642
Publication state
Published
Issued date
06/2004
Volume
30
Number
6
Pages
1204-11
Language
english
Notes
Le Berre, Rozenn
Faure, Karine
Fauvel, Harold
Viget, Nathalie B
Ader, Florence
Prangere, Thierry
Thomas, Anne Marie
Leroy, Xavier
Pittet, Jean-Francois
Marchetti, Philippe
Guery, Benoit P
eng
Evaluation Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Intensive Care Med. 2004 Jun;30(6):1204-11. doi: 10.1007/s00134-004-2165-0. Epub 2004 Feb 26.
Abstract
OBJECTIVE: Pseudomonas aeruginosa-induced lung injury is characterized not only by the alteration in lung fluid movement but also by apoptosis of lung epithelial and endothelial cells. We studied whether inhibition of apoptosis using a broad spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD.fmk), would affect lung fluid balance in rat P. aeruginosa pneumonia. METHODS: Z-VAD.fmk (3 mg/kg) was administered intravenously simultaneously with P. aeruginosa intratracheal instillation (0.5 ml/kg, 2 x 10(9) CFU/ml). Apoptosis was evaluated with the TUNEL technique, cytoplasmic oligonucleosome assay, and caspase 3 activation. To evaluate lung permeability, extravascular plasma equivalent (EPE) and lung wet to dry weight ratio (W/D) were measured 4 h after intratracheal instillation of P. aeruginosa. RESULTS: We found an increase of lung apoptosis 4 h after P. aeruginosa instillation: cytoplasmic oligonucleosome assay increased from 3.17+/-0.78 to 26.82+/-4.67 ODx1000/mg of proteins/ml, Z-VAD.fmk administration decreased this parameter to 10.3+/-2.98 ODx1000/mg of proteins/ml. Caspase 3 levels followed the same pattern. Apoptosis involved both epithelial cells and endothelial cells. Endothelial permeability was increased after Pseudomonas instillation: W/D increased from 3.75+/-0.28 in the Co group to 4.42+/-0.23 in the Pn group; EPE was also higher in the Pn group compared with the Co group (0.125+/-0.04 and 0.002+/-0.01 ml, respectively). Both of these parameters were improved after Z-VAD.fmk administration; W/D decreased to 3.36+/-0.25 and EPE to 0.02+/-0.02 ml. CONCLUSION: Apoptosis occurs in the early phase of P. aeruginosa pneumonia. Administration of Z-VAD.fmk significantly decreases DNA fragmentation and caspase 3 levels. This is associated with an improvement of endothelial permeability and lung fluid balance.
Keywords
Amino Acid Chloromethyl Ketones/*pharmacology, Animals, Apoptosis/*drug effects/physiology, Capillary Permeability/drug effects, Endothelium, Vascular/drug effects/metabolism, Pseudomonas Infections/*physiopathology, Pulmonary Alveoli/drug effects/metabolism, Pulmonary Edema/*physiopathology, Rats, Rats, Sprague-Dawley, Respiratory Distress Syndrome/*physiopathology, Statistics, Nonparametric
Pubmed
Create date
29/04/2021 10:59
Last modification date
30/04/2021 6:38
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