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Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury.
Am J Respir Crit Care Med. 2006 May 15; 173(10):1130-8.AJ

Abstract

RATIONALE

Acute inflammation and vascular leak are cardinal features of acute lung injury and the acute respiratory distress syndrome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components.

OBJECTIVE

To test the hypothesis that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) may attenuate the acute lung inflammatory response to lipopolysaccharide (LPS) and enhance lung vascular barrier recovery, we used in vivo and in vitro models of LPS-induced lung injury.

METHODS

Rats received intratracheal aerosolized LPS (5 mg/kg) or sterile water with concurrent intravenous injection of OxPAPC (0.5-6.0 mg/kg) or saline alone. Nonoxidized PAPC was used as a control. At 18 h, bronchoalveolar lavage was performed and the lungs were removed for histologic analysis. Measurements of endothelial transmonolayer electrical resistance and immunofluorescent analysis of monolayer integrity were used in an in vitro model of LPS-induced lung vascular barrier dysfunction.

MEASUREMENTS AND MAIN RESULTS

In vivo, aerosolized intratracheal LPS induced lung injury with profound increases in bronchoalveolar lavage neutrophils, protein content, and the inflammatory cytokines interleukin 6 and interleukin 1beta, as well as tissue neutrophils. OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses. In vitro, oxidized phospholipids attenuated LPS-induced endothelial barrier disruption and reversed LPS-induced cytoskeletal remodeling and disruption of monolayer integrity.

CONCLUSIONS

These studies demonstrate in vivo and in vitro protective effects of oxidized phospholipids on LPS-induced lung dysfunction.

Authors+Show Affiliations

Division of Pulmonary and Critical Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16514111

Citation

Nonas, Stephanie, et al. "Oxidized Phospholipids Reduce Vascular Leak and Inflammation in Rat Model of Acute Lung Injury." American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 10, 2006, pp. 1130-8.
Nonas S, Miller I, Kawkitinarong K, et al. Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury. Am J Respir Crit Care Med. 2006;173(10):1130-8.
Nonas, S., Miller, I., Kawkitinarong, K., Chatchavalvanich, S., Gorshkova, I., Bochkov, V. N., Leitinger, N., Natarajan, V., Garcia, J. G., & Birukov, K. G. (2006). Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury. American Journal of Respiratory and Critical Care Medicine, 173(10), 1130-8.
Nonas S, et al. Oxidized Phospholipids Reduce Vascular Leak and Inflammation in Rat Model of Acute Lung Injury. Am J Respir Crit Care Med. 2006 May 15;173(10):1130-8. PubMed PMID: 16514111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury. AU - Nonas,Stephanie, AU - Miller,Ian, AU - Kawkitinarong,Kamon, AU - Chatchavalvanich,Santipongse, AU - Gorshkova,Irina, AU - Bochkov,Valery N, AU - Leitinger,Norbert, AU - Natarajan,Viswanathan, AU - Garcia,Joe G N, AU - Birukov,Konstantin G, Y1 - 2006/03/02/ PY - 2006/3/4/pubmed PY - 2006/6/23/medline PY - 2006/3/4/entrez SP - 1130 EP - 8 JF - American journal of respiratory and critical care medicine JO - Am J Respir Crit Care Med VL - 173 IS - 10 N2 - RATIONALE: Acute inflammation and vascular leak are cardinal features of acute lung injury and the acute respiratory distress syndrome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components. OBJECTIVE: To test the hypothesis that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) may attenuate the acute lung inflammatory response to lipopolysaccharide (LPS) and enhance lung vascular barrier recovery, we used in vivo and in vitro models of LPS-induced lung injury. METHODS: Rats received intratracheal aerosolized LPS (5 mg/kg) or sterile water with concurrent intravenous injection of OxPAPC (0.5-6.0 mg/kg) or saline alone. Nonoxidized PAPC was used as a control. At 18 h, bronchoalveolar lavage was performed and the lungs were removed for histologic analysis. Measurements of endothelial transmonolayer electrical resistance and immunofluorescent analysis of monolayer integrity were used in an in vitro model of LPS-induced lung vascular barrier dysfunction. MEASUREMENTS AND MAIN RESULTS: In vivo, aerosolized intratracheal LPS induced lung injury with profound increases in bronchoalveolar lavage neutrophils, protein content, and the inflammatory cytokines interleukin 6 and interleukin 1beta, as well as tissue neutrophils. OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses. In vitro, oxidized phospholipids attenuated LPS-induced endothelial barrier disruption and reversed LPS-induced cytoskeletal remodeling and disruption of monolayer integrity. CONCLUSIONS: These studies demonstrate in vivo and in vitro protective effects of oxidized phospholipids on LPS-induced lung dysfunction. SN - 1073-449X UR - https://www.unboundmedicine.com/medline/citation/16514111/Oxidized_phospholipids_reduce_vascular_leak_and_inflammation_in_rat_model_of_acute_lung_injury_ L2 - https://www.atsjournals.org/doi/10.1164/rccm.200511-1737OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -