Neutrophil Inhibitory Factor Selectively Inhibits the Endothelium-Driven Transmigration of Eosinophils In Vitro and Airway Eosinophilia in OVA-Induced Allergic Lung Inflammation. (4th December 2012)

• Record Type: Journal Article
• Authors: Schnyder-Candrian, Silvia; Maillet, Isabelle; Le Bert, Marc; Brault, Lea; Jacobs, Muazzam; Ryffel, Bernhard; Schnyder, Bruno; Moser, René
• Other Names: Leite-de-Moraes Maria Academic Editor.
• Is Part Of: Journal of allergy. Volume 2012(2012)
• Publication Date: 2012-12-04
• Subjects: Allergy -- Periodicals; Immunologic diseases -- Periodicals; Allergy and Immunology; Hypersensitivity; Immune System Diseases; Allergy; Immunologic diseases; Electronic journals; Periodical; Periodicals; 616.97
• DOI: 10.1155/2012/245909
• Languages: English
• ISSNs: 1687-9783

Abstract

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 : 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.