Neutrophil Inhibitory Factor Selectively Inhibits the Endothelium-Driven Transmigration of EosinophilsIn Vitroand Airway Eosinophilia in OVA-Induced Allergic Lung Inflammation
| Autor: | Silvia Schnyder-Candrian, Muazzam Jacobs, René Moser, Bernhard Ryffel, Marc Le Bert, Lea Brault, Bruno Schnyder, Isabelle Maillet |
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| Přispěvatelé: | Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO) |
| Rok vydání: | 2012 |
| Předmět: |
Article Subject
Leukocyte adhesion molecule Inflammation CD18 [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity Umbilical vein 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy Eosinophilia 030304 developmental biology 0303 health sciences business.industry respiratory system Eosinophil Molecular biology 3. Good health Endothelial stem cell medicine.anatomical_structure Immunology Tumor necrosis factor alpha medicine.symptom business 030217 neurology & neurosurgery Research Article |
| Zdroj: | Asian Pacific journal of allergy and immunology Asian Pacific journal of allergy and immunology, Allergy and Immunology Society of Thailand, 2012, 2012, pp.1-10. ⟨10.1155/2012/245909⟩ Journal of Allergy |
| ISSN: | 1687-9791 1687-9783 0125-877X |
| DOI: | 10.1155/2012/245909 |
| Popis: | Leukocyte adhesion molecules are involved in cell recruitment in an allergic airway response and therefore provide a target for pharmaceutical intervention. Neutrophil inhibitory factor (NIF), derived from canine hookworm (Ancylostoma caninum), binds selectively and competes with the A-domain of CD11b for binding to ICAM-1. The effect of recombinant NIF was investigated. Intranasal administration of rNIF reduced pulmonary eosinophilic infiltration, goblet cell hyperplasia, and Th2cytokine production in OVA-sensitized mice.In vitro, transendothelial migration of human blood eosinophils across IL-4-activated umbilical vein endothelial cell (HUVEC) monolayers was inhibited by rNIF (IC50:4.6±2.6 nM; mean ± SEM), but not across TNF or IL-1-activated HUVEC monolayers. Treatment of eosinophils with rNIF together with mAb 60.1 directed against CD11b or mAb 107 directed against the metal ion-dependent adhesion site (MIDAS) of the CD11b A-domain resulted in no further inhibition of transendothelial migration suggesting shared functional epitopes. In contrast, rNIF increased the inhibitory effect of blocking mAbs against CD18, CD11a, and VLA-4. Together, we show that rNIF, a selective antagonist of the A-domain of CD11b, has a prominent inhibitory effect on eosinophil transendothelial migrationin vitro, which is congruent to thein vivoinhibition of OVA-induced allergic lung inflammation. |
| Databáze: | OpenAIRE |
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