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| Contact |
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Schnyder Bruno |
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| Title |
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Neutrophil inhibitory factor selectively inhibits the endothelium-driven transmigration of eosinophils in vitro and airway eosinophilia in OVA-induced allergic lung inflammation |
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Silvia Schnyder-Candrian, Isabelle Maillet, Bernard Ryffel, Bruno Schnyder, R. Moser, Marc Le Bert, Lea Brault and Muazzam Jacobs |
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| References |
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Journal of Allergy, 2012 (2012), Article ID 245909, 10 pages |
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| Url |
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http://dx.doi.org/10.1155/2012/245909 |
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| Abstract |
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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 Th2 cytokine 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 migration in vitro, which is congruent to the in vivo inhibition of OVA-induced allergic lung inflammation. |
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