title: Regulation of allergic lung inflammation by endothelial cell transglutaminase 2.
abstract: Tissue transglutaminase 2 (TG2) is an enzyme with multiple functions, including catalysis of serotonin conjugation to proteins (serotonylation). Previous research indicates that TG2 expression is upregulated in human asthma and in the lung endothelium of ovalbumin (OVA)-challenged mice. It is not known whether endothelial cell TG2 is required for allergic inflammation. Therefore, to determine whether endothelial cell TG2 regulates allergic inflammation, mice with an endothelial cell-specific deletion of TG2 were generated, and these mice were sensitized and challenged in the airways with OVA. Deletion of TG2 in endothelial cells blocked OVA-induced serotonylation in lung endothelial cells, but not lung epithelial cells. Interestingly, deletion of endothelial TG2 reduced allergen-induced increases in respiratory system resistance, number of eosinophils in the bronchoalveolar lavage, and number of eosinophils in the lung tissue. Endothelial cell deletion of TG2 did not alter expression of adhesion molecules, cytokines, or chemokines that regulate leukocyte recruitment, consistent with other studies, demonstrating that deletion of endothelial cell signals does not alter lung cytokines and chemokines during allergic inflammation. Taken together, the data indicate that endothelial cell TG2 is required for allergic inflammation by regulating the recruitment of eosinophils into OVA-challenged lungs. In summary, TG2 functions as a critical signal for allergic lung responses. These data identify potential novel targets for intervention in allergy/asthma.
authors.affiliation: Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois;
authors.forename: Frank
authors.initials: F
authors.lastname: Soveg
authors.affiliation: Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois;
authors.forename: Hiam
authors.initials: H
authors.lastname: Abdala-Valencia
authors.affiliation: Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois;
authors.forename: Jackson
authors.initials: J
authors.lastname: Campbell
authors.affiliation: Pulmonary Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and.
authors.forename: Luisa
authors.initials: L
authors.lastname: Morales-Nebreda
authors.affiliation: Pulmonary Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Gökhan M
authors.initials: GM
authors.lastname: Mutlu
authors.affiliation: Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois; j-cook-mills@northwestern.edu.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Cook-Mills
mesh_terms: D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology*; D004804:Eosinophils / Q000276:immunology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D008168:Lung / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000502:physiology*
chemical_list: D018925:Chemokines; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: airway responsiveness; allergy; endothelium; lung; transglutaminase 2