P2Y2 receptor regulates VCAM-1 membrane and soluble forms and eosinophil accumulation during lung inflammation.
ATP has been defined as a key mediator of asthma. In this study, we evaluated lung inflammation in mice deficient for the P2Y(2) purinergic receptor. We observed that eosinophil accumulation, a distinctive feature of lung allergic inflammation, was defective in OVA-treated P2Y(2)-deficient mice compared with OVA-treated wild type animals. Interestingly, the upregulation of VCAM-1 was lower on lung endothelial cells of OVA-treated P2Y(2)(-/-) mice compared with OVA-treated wild type animals. Adhesion assays demonstrated that the action of UTP on leukocyte adhesion through the regulation of endothelial VCAM-1 was abolished in P2Y(2)-deficient lung endothelial cells. Additionally, the level of soluble VCAM-1, reported as an inducer of eosinophil chemotaxis, was strongly reduced in the bronchoalveolar lavage fluid (BALF) of P2Y(2)-deficient mice. In contrast, we observed comparable infiltration of macrophages and neutrophils in the BALF of LPS-aerosolized P2Y(2)(+/+) and P2Y(2)(-/-) mice. This difference could be related to the much lower level of ATP in the BALF of LPS-treated mice compared with OVA-treated mice. Our data define P2Y(2) as a regulator of membrane and soluble forms of VCAM-1 and eosinophil accumulation during lung inflammation.
Vanderstocken
Gilles
G
Institute of Interdisciplinary Research, Erasme Hospital, Free University of Brussels, Brussels, Belgium.
Bondue
Benjamin
B
Horckmans
Michael
M
Di Pietrantonio
Larissa
L
Robaye
Bernard
B
Boeynaems
Jean-Marie
JM
Communi
Didier
D
D055371:Acute Lung Injury / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D020033:Protein Isoforms / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058473:Receptors, Purinergic P2Y2 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*
D008070:Lipopolysaccharides; D020033:Protein Isoforms; D058473:Receptors, Purinergic P2Y2; D019010:Vascular Cell Adhesion Molecule-1; D010047:Ovalbumin