Semaphorin 7A is expressed on airway eosinophils and upregulated by IL-5 family cytokines.
Résumé
Semaphorin 7A (sema7a) plays a major role in TGF-β1-induced lung fibrosis. Based on the accumulating evidence that eosinophils contribute to fibrosis/remodeling in the airway, we hypothesized that airway eosinophils may be a significant source of sema7a. In vivo, sema7a was expressed on the surface of circulating eosinophils and upregulated on bronchoalveolar lavage eosinophils obtained after segmental bronchoprovocation with allergen. Based on mRNA levels in unfractionated and isolated bronchoalveolar cells, eosinophils are the predominant source of sema7a. In vitro, among the members of the IL-5-family cytokines, sema7a protein on the surface of blood eosinophils was increased more by IL-3 than by GM-CSF or IL-5. Cytokine-induced expression of cell surface sema7a required translation of newly synthesized protein. Finally, a recombinant sema7a induced alpha-smooth muscle actin production in human bronchial fibroblasts. semaphorin 7A is a potentially important modulator of eosinophil profibrotic functions in the airway remodeling of patients with chronic asthma.
Mots clés
Actins
Allergens
Antigens, CD
Bronchoalveolar Lavage Fluid
CD4-Positive T-Lymphocytes
Cells, Cultured
Eosinophils
Fibroblasts
GPI-Linked Proteins
Humans
Hypersensitivity
Interleukin-5
Lung
Semaphorins
Up-Regulation
BAL
EOS
Eosinophil
Fibrosis
IL-3
RT-qPCR
SBP-Ag
Sema7a
Semaphorin 7A
Translation
bronchoalveolar lavage
eosinophils
real-time quantitative PCR
segmental bronchoprovocation with allergen
semaphorin 7A.