期刊
BLOOD
卷 109, 期 10, 页码 4280-4287出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-08-039255
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资金
- NHLBI NIH HHS [HL57345, P01 HL057345] Funding Source: Medline
- NIAID NIH HHS [R01 AI072115, AI33977, R01 AI038425, R37 AI038425, AI38425] Funding Source: Medline
CD33-related Siglecs (CD33rSigiecs) are a family of sialic acid-recognizing lectins on immune cells whose biologic functions are unknown. We studied in vivo functions of Siglec-F, the CD33rSiglec expressed on mouse eosinophils, which are prominent in allergic processes. Induction of allergic lung inflammation in mice caused up-regulation of Siglec-IF on blood and bone marrow eosinophils, accompanied by newly induced expression on some CD4(+) cells, as well as quantitative up-regulation of endogenous Siglec-F ligands in the lung tissue and airways. Taken together with the tyrosine-based inhibitory motif in the cytosolic tall of Siglec-F, the data suggested a negative feedback loop, controlling allergic responses of eosinophils and helper T cells, via Siglec-F and Siglec-F ligands. To pursue this hypothesis, we created Siglec-F-null mice. Allergen-challenged null mice showed increased lung eosinophil infiltration, enhanced bone marrow and blood eosinophilia, delayed resolution of lung eosinophilia, and reduced peribronchial-cell apoptosis. Anti-Siglec-F antibody cross-linking also enhanced eosinophil apoptosis in vitro. These data support the proposed negative feedback role for Siglec-F, represent the first in vivo demonstration of biologic functions for any CD33rSiglec, and predict a role for human Siglec-8 (the isofunctional paralog of mouse Siglec-F) in regulating the pathogenesis of human eosinophil-mediated disorders.
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