Siglec-F-dependent negative regulation of allergen-induced eosinophilia depends critically on the experimental model.
Siglec-8 and siglec-F are paralogous membrane proteins expressed on human and murine eosinophils respectively. They bind similar sialylated and sulphated glycans and mediate eosinophil apoptosis when cross-linked with antibodies or glycan ligands. In models of allergic eosinophilic airway inflammation, siglec-F was shown previously to be important for negatively regulating eosinophilia. It was proposed that this was due to siglec-F-dependent apoptosis, triggered via engagement with ligands that are upregulated on bronchial epithelium. Our aim was to further investigate the functions of siglec-F by comparing two commonly used models of ovalbumin-induced airway inflammation that differ in the dose and route of administration of ovalbumin. In confirmation of published results, siglec-F-deficient mice had enhanced lung tissue eosinophilia in response to intranasal ovalbumin delivered every other day. However, following aerosolised ovalbumin delivered daily, there was no influence of siglec-F deficiency on lung eosinophilia. Expression of siglec-F ligands in lung tissues was similar in both models of allergen induced inflammation. These data demonstrate that siglec-F-dependent regulation of eosinophilia is subtle and depends critically on the model used. The findings also indicate that mechanisms other than ligand-induced apoptosis may be important in siglec-F-dependent suppression of eosinophilia.
Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK, DD1 5EH.
Sarah J
SJ
McMillan
Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK, DD1 5EH.
Hannah E
HE
Richards
Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK, DD1 5EH. Electronic address: p.r.crocker@dundee.ac.uk.
Paul R
PR
Crocker
D000485:Allergens / Q000276:immunology*; D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D023061:Gene Order; D018390:Gene Targeting; D056426:Genetic Loci; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011485:Protein Binding; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins
D000485:Allergens; D015214:Antigens, Differentiation, Myelomonocytic; D008024:Ligands; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C443130:Siglecf protein, mouse
Allergic airway inflammation; Eosinophil; Siglec-8; Siglec-F