Detection of the chemokine RANTES and endothelial adhesion molecules in nasal polyps

Background: To better understand the mechanisms of eosinophil recruitment into the upper airways, we examined human nasal polyps for the expression of the chemotactic cytokine RANTES and the endothelial adhesion molecules E-selectin and vascular cell adhesion molecule-1 (VCAM-1). Methods: Routine histologic examination and immunostaining with antibodies to RANTES. E-selectin, and VCAM-1 were performed on three types of tissues: nasal polyps, sinus mucosa, or turbinates from patients undergoing other elective procedures (S/T), and nasal biopsy specimens form nonallergic volunteers (NA). To further quantify the expression of endothelial adhesion molecules, some tissue samples were homogenized, and the resulting supernatants were assayed with sandwich ELISAs for VCAM-1 and E-selectin. Results: Polyp eosinophil counts ranged from 19/m² to 1818/mm² (763 ± 120/mm², mean ± SEM) and were significantly higher than those found in the control tissues (5 ± 2 in S/T samples and 20 ± 9 in NA samples, p < 0.002). Immunocytochemical staining for RANTES was observed in 11 of 14 polyps; intense staining for RANTES (grade 3) was observed in six of 14 polyps. None of nine S/T samples or five NA samples demonstrated grade 3 staining. Staining with anti-RANTES was largely localized to airway and grandular epithelium. There was no significant correlation between counts of eosinophils or the combined total of eosinophils plus mononuclear cells and the intensity of epithelial RANTES staining in all nasal tissues. Staining for VCAM-1, as well as for E- selectin, was detected in 11 of 14 polyps and eight of 13 control tissues. VCAM-1 detected by ELISA in polyp tissues (6.8 ± 1.3 μg/gm) was higher than that found in six S/T samples (1.2 ± 0.3 μg/gm, p < 0.005) and in two NA samples (1.8 ± 0.02 μg/gm, p = 0.08). E-selectin values in polyps (1.4 ± 0.3 μg/gm) were not statistically different from those detected in six S/T samples (0.5 ± 0.2 μg/gm) or two NA samples (1.6 ± 0.4 μg/gm). Counts of eosinophils and eosinophils plus mononuclear cells displayed a strong correlation with VCAM-1 ELIZA values (p < 0.005) and p < 0.004, respectively) but not with VCAM-1 staining. VCAM-1 staining correlated with EG2-positive eosinophils in nasal polyp tissues (p < 0.01). E-selectin staining did not correlate with either neutrophil or eosinophil counts. Conclusions: These studies demonstrate that the chemokine RANTES is produced in vivo and is localized predominantly to nasal epithelium. Endothelial activation, as indicated by adhesion molecule expression, occurs in human nasal polyp tissues and in controls tissues, possibly reflecting the continued antigen exposure of the nasal antigen exposure of the nasal mucosa. The correlations found in this study suggest that expression of VCAM-1 plays a role in the selective recruitment of eosinophils and mononuclear cells into nasal polyp tissues and that RANTES may be more important in localizing eosinophils to the epithelium.