Role of interleukin-4 and vascular cell adhesion molecule-1 in selective eosinophil migration into the airways in allergic asthma.

Abstract

Recent in vitro studies have suggested that interleukin-4 (IL-4) may be involved in the preferential migration of eosinophils into the airways in allergic asthma through its capacity to selectively increase vascular cell adhesion molecule-1 (VCAM-1) expression on vessels. To test this hypothesis, we studied the expression of VCAM-1, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) on vascular endothelium in bronchial mucosal biopsies from 20 allergic asthmatics using an immunohistochemistry technique and related the observations to IL-4 levels in bronchoalveolar lavage (BAL) fluid simultaneously obtained and to eosinophil infiltration in the bronchial mucosa. IL-4 was detectable in BAL fluid from nine subjects (range, 15.1 to 110 pg/ml in 20-fold concentrated BAL fluid) (IL-4-positive asthmatics) but unmeasurable in the remaining 11 subjects (IL-4-negative asthmatics). The IL-4-positive asthmatics showed a significantly increased expression of VCAM-1 but not E-selectin and ICAM-1 on vessels as compared with both IL-4-negative asthmatics (P < 0.001) and diseased control subjects (P < 0.001). In asthmatics, VCAM-1 expression was positively correlated with BAL IL-4 levels (rs = 0.89; P < 0.0001). Moreover, there was a significant correlation between the endothelial expression of VCAM-1 and the number of eosinophils, but not neutrophils, in the bronchial submucosa (r2 = 0.76; P < 0.001). A significant correlation was also found between BAL IL-4 levels and the number of eosinophils. These results suggest that IL-4 is a VCAM-1-selective activator also in human airways and the VCAM-1-dependent pathways play a role in selective migration of eosinophils into the airways in allergic asthma, and support the hypothesis described above.

Allergen-induced airway disease is mouse strain dependent

“…IL-4 also has other biological effects in the allergic response it shares with IL-13. Both IL-4 and IL-13 are believed to increase the expression of vascular cell adhesion molecule-1 on endothelial cells, which facilitates the recruitment of eosin-ophils (11). In the present study, six of the nine strains of mice [BTBRϩ(T)/tf/tf, A/J, DBA/2J, BALB/cJ, C57BL/6J, and 129/SvIm] had significantly increased levels of IL-4 in the whole lung lavage fluid.…”

Eotaxin Expression by Epithelial Cells and Plasma Cells in Chronic Asthma

“…In human asthma, increased expression of various eosinophil-selective chemoattractants has been re-ported (Alam et al, 1996;Lamkhioued et al, 1997;Tillie-Leblond et al, 2000;Ying et al, 1999) and increased expression of VCAM-1 (Fukuda et al, 1996) has been demonstrated. However, the inherent difficulty of human studies has made it difficult to assess the relative importance of different mediators and mechanisms during the evolution of an allergic inflammatory response.…”

Increased levels of surfactant protein A and D in bronchoalveolar lavage fluids in patients with bronchial asthma

“…Therefore, the authors asked firstly whether the levels of surfactant associated proteins in the bronchoalveolar lavage (BAL) fluid would be altered in patients with bronchial asthma. To answer the question for local production of surfactant proteins in the airways, the composition of surfactant proteins in the first lavage as bronchial lavage (BL) and the second and third lavages consecutively as alveolar lavages (AL) were investigated separately [10,11]. The co-relationships in the BL between the amounts of surfactant proteins and those of fucose, which is thought to be one of the markers of submucosal secretion were also analysed.…”