Protective effect of purinergic agonist ATPγS against acute lung injury

Irina A. Kolosova, Tamara Mirzapoiazova, Liliana Moreno-Vinasco, Saad Sammani, Joe G N Garcia, Alexander Dmitriyevich Verin

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of acute respiratory failure associated with high morbidity and mortality. Although ALI/ARDS pathogenesis is only partly understood, pulmonary endothelium plays a major role by regulating lung fluid balance and pulmonary edema formation. Consequently, endothelium-targeted therapies may have beneficial effects in ALI/ARDS. Recently, attention has been given to the therapeutic potential of purinergic agonists and antagonists for the treatment of cardiovascular and pulmonary diseases. Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface P2Y receptors. We previously described ATP-induced endothelial cell (EC) barrier enhancement via a complex cell signaling and hypothesized endothelial purinoreceptors activation to exert anti-inflammatory barrier-protective effects. To test this hypothesis, we used a murine model of ALI induced by intratracheal administration of endotoxin/lipopolysaccharide (LPS) and cultured pulmonary EC. The nonhydrolyzed ATP analog ATPγS (50-100 μM final blood concentration) attenuated inflammatory response with decreased accumulation of cells (48%, P < 0.01) and proteins (57%, P < 0.01) in bronchoalveolar lavage and reduced neutrophil infiltration and extravasation of Evans blue albumin dye into lung tissue. In cell culture model, ATPγS inhibited junctional permeability induced by LPS. These findings suggest that purinergic receptor stimulation exerts a protective role against ALI by preserving integrity of endothelial cell-cell junctions.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume294
Issue number2
DOIs
StatePublished - Feb 1 2008

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Purinergic Agonists
Acute Lung Injury
Adult Respiratory Distress Syndrome
Lung
Endothelial Cells
Adenosine Triphosphate
Endothelium
Lipopolysaccharides
Purinergic Antagonists
Purinergic Receptors
Pyrimidines
Evans Blue
Purines
Uridine Triphosphate
Uridine Diphosphate
Water-Electrolyte Balance
Intercellular Junctions
Neutrophil Infiltration
Cell Surface Receptors
Bronchoalveolar Lavage

Keywords

  • Endothelial barrier
  • Endotoxin/lipopolysaccharide
  • Inflammation
  • Mice

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Protective effect of purinergic agonist ATPγS against acute lung injury. / Kolosova, Irina A.; Mirzapoiazova, Tamara; Moreno-Vinasco, Liliana; Sammani, Saad; Garcia, Joe G N; Verin, Alexander Dmitriyevich.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 294, No. 2, 01.02.2008.

Research output: Contribution to journalArticle

Kolosova, Irina A. ; Mirzapoiazova, Tamara ; Moreno-Vinasco, Liliana ; Sammani, Saad ; Garcia, Joe G N ; Verin, Alexander Dmitriyevich. / Protective effect of purinergic agonist ATPγS against acute lung injury. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2008 ; Vol. 294, No. 2.
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