A role for Bid in eosinophil apoptosis and in allergic airway reaction.
Bid, a proapoptotic member of Bcl-2 family, is involved in Fas receptor signaling. Fas activation promotes human eosinophil cell death and is believed to accelerate the resolution of pulmonary Th2-driven allergic reaction in mice. We hypothesized that Bid would regulate eosinophil apoptosis and Ag-induced airway inflammation, particularly eosinophilia. C57BL/6 Bid(-/-) and wild-type mice were immunized and repeatedly challenged with OVA, and bronchoalveolar lavage (BAL) fluid, lung, and spleen were collected 4-240 h after the final challenge. Cultured BAL eosinophils from Bid-deficient mice showed resistance to Fas-mediated apoptotic DNA fragmentation, phosphatidylserine exposure, mitochondria depolarization, and caspase-3 activity. In addition, OVA-challenged Bid(-/-) mice had higher BAL eosinophilia and a lower proportion of BAL apoptotic eosinophils than Bid(+/+) mice. This was accompanied by augmented BAL levels of the eosinophilotactic cytokine, IL-5, and of the eosinophil-associated mediators, TGF-beta1 and fibronectin. Finally, cultured OVA-stimulated lung mononuclear cells and splenocytes from Bid-deficient mice showed increased release of the Th2-type cytokines, IL-4 and IL-5, but no change in cell number. We conclude that Bid modulates BAL eosinophilia by regulating both eosinophil apoptosis and Th2-type cytokine production.
Maret
Marielle
M
Institut National de la Santé et de la Recherche Médicale Unité 700 and Université Paris Diderot-Paris 7, Paris, France.
Ruffié
Claude
C
Létuvé
Séverine
S
Phelep
Aurélie
A
Thibaudeau
Olivier
O
Marchal
Joëlle
J
Pretolani
Marina
M
Druilhe
Anne
A
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators