Role of the Mac-1 and VLA-4 integrins, and concomitant Th2-cytokine production, in nitric oxide modulated eosinophil migration from bone marrow to lungs in allergic mice

Abstract

Although numerous studies demonstrate the participation of nitric oxide (NO) in various inflammatory diseases, the precise function of NO in allergic asthma remains unclear. We investigated whether iNOS inhibition could interfere with the kinetics of VLA-4 and Mac-1 expression and adhesion properties of bone marrow and peripheral blood eosinophils of sensitized mice after antigen exposure. Treatment of allergic mice with 1400 W (iNOS inhibitor) increased the adhesion of bone marrow eosinophils to ICAM-1, but not blood eosinophils, at 24h and 48 h after OVA-challenge. Conversely, adhesion of blood eosinophils from 1400 W-treated mice to VCAM-1 diminished at 24h and was almost completely blocked at 48 h. 1400 W did not induce any change in the adhesion of bone marrow eosinophils to VCAM-1, at 24h, but cells collected 48 h after challenge showed significantly lower adherence. Flow cytometry demonstrated that 1400 W resulted in a significantly increased Mac-1 expression on bone marrow eosinophils at 24h, as compared to control mice. However, at 24h, 1400 W significantly decreased Mac-1 and VLA-4 expressions on blood eosinophils. At 48 h, the expressions of both Mac-1 and VLA-4 returned to previous levels. Results show a temporal effect of iNOS upon Mac-1 expression and function, the chief adhesion molecule involved in the eosinophil efflux from the bone marrow at 24h. In contrast, Mac-1 and VLA-4 were involved in eosinophil mobilization from blood to lungs at 48 h after antigen challenge. Data suggest an important role of the Mac-1 and VLA-4 in the iNOS-modulated migration of eosinophils to the lungs of allergic mice.

Predictive Value of Nasal Nitric Oxide and Serum NOS2 Levels in the Efficacy of Subcutaneous Immunotherapy in Pediatric Patients with Allergic Rhinitis

“…As a common upper airway inflammatory disease, AR is typically characterized by a predominant Th2 response and eosinophil infiltration in nasal mucosa [ 32 – 34 ]. NO was proven to be pivotal in modulating the production of Th2 cytokines which were responsible for the migration of eosinophils into the airway mucosa [ 35 ]. Prior publications demonstrated that nNO could be used as a reproducible and noninvasive biomarker in respiratory diseases [ 36 , 37 ].…”

Control of myeloid cell functions by nociceptors

“…They localize close to sensory as well as parasympathetic neurons both in animal models of asthma and in biopsied lungs of asthma patients (223). In prurigo nodularis, a chronic skin disease characterized by nodules and intense itch, eosinophils are closely associated with CGRP + nociceptive fibers (224) and in atopic dermatitis patients eosinophils are more closely associated with nerve fibers than in healthy controls (225). Finally, although the identity of the neurons was not determined in this context, close nerve-eosinophil contact was also observed in the colon and Peyer's patches of rats infected with the parasite Fasciola hepatica (226).…”

Mucosal Eosinophils

“…This same study also showed a dynamic expression of α 4 β 7 on eosinophils across different tissue contexts. The findings that eotaxin-1-induced eosinophil recruitment to the lung and eotaxin-1-mediated chemoattraction in vitro are dependent upon VLA-4 (α 4 β 1 ) (Kitayama et al, 1997) and that VLA-4 is dynamically modulated by allergen challenge (Pelaquini et al, 2011) suggest that the other α 4 -associated integrins on eosinophils (e.g., α 4 β 7 ) may also be involved in eotaxin-mediated events. Consistent with this possibility, there is delayed intestinal hypersensitivity (including lymphocyte and eosinophil infiltrations) in response to intestinal infection with Trichinella spiralis in β 7 -deficient animals (Artis et al, 2000).…”