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Journal of Allergy
Volume 2012 (2012), Article ID 245909, 10 pages
http://dx.doi.org/10.1155/2012/245909
Research Article

Neutrophil Inhibitory Factor Selectively Inhibits the Endothelium-Driven Transmigration of Eosinophils In Vitro and Airway Eosinophilia in OVA-Induced Allergic Lung Inflammation

1UMR7355, CNRS, Orleans, France
2Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France
3Institute for Clinical and Biomedical Research Thurgau, 9548 Matzingen, Switzerland
4Institute of Infectious Disease and Molecular Medicine (IIDMM), University of Cape Town, Cape Town, South Africa
5UAS, HES-SO, Route de Rawyl 47, 1950 Sion, Switzerland
6IBR Inc., Institute for Biopharmaceutical Research, Lauchefeld, 9548 Matzingen, Switzerland

Received 9 June 2012; Accepted 30 August 2012

Academic Editor: Maria Leite-de-Moraes

Copyright © 2012 Silvia Schnyder-Candrian et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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:  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.