Monocyte chemotactic proteins in allergen-induced inflammation in the nasal mucosa: effect of topical corticosteroids.
BACKGROUND
Human allergen-induced rhinitis is associated with the recruitment and activation of inflammatory cells, particularly eosinophils and CD4(+) T cells, in the nasal mucosa. Chemokines are inflammatory mediators capable of attracting specific inflammatory cell populations. Monocyte chemotactic proteins (MCPs), a subfamily of CC chemokines, have been shown to induce chemotactic activity particularly in eosinophils, T cells, and monocytes under in vitro assay conditions.


OBJECTIVE
To assess the contribution of MCPs in the recruitment of inflammatory cells in vivo, we investigated the allergen-induced late response in subjects with allergic rhinitis.


METHODS
Patients were randomized to receive a 6-week treatment with either topical corticosteroid (n = 6) or a matched placebo (n = 6). Nasal inferior turbinate biopsy specimens were obtained from all subjects before and during allergen-induced late responses. By using immunocytochemistry, tissue sections were examined for the presence of MCP-1, MCP-3, and MCP-4 and for the phenotype of infiltrating cells within the nasal mucosa. In addition, double sequential immunocytochemistry was used to confirm the phenotype of MCP-immunoreactive positive cells. Furthermore, the effect of topical corticosteroids on the expression of MCPs and on the cellular infiltrate was also examined.


RESULTS
MCP-1, MCP-3, and MCP-4 were expressed in all the baseline samples, with prominent staining observed within the nasal epithelium. Biopsy specimens taken after challenge exhibited significant upregulation in the expression of MCP-3 and MCP-4 (P <.001). On the other hand, this increase in response to allergen was reduced in patients pretreated with topical corticosteroids. Colocalization experiments revealed that the majority of MCP+ cells in the subepithelium were macrophages, followed by T cells and eosinophils.


CONCLUSIONS
Our results demonstrate that allergen-induced rhinitis is associated with an increased expression of MCP-3 and MCP-4, which may be closely related to the influx of inflammatory cells and may thus contribute to the pathogenesis of allergic rhinitis.
Christodoulopoulos
P
P
Meakins-Christie Laboratories, Montreal, Quebec, Canada.
Wright
E
E
Frenkiel
S
S
Luster
A
A
Hamid
Q
Q
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000485:Allergens / Q000009:adverse effects; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D054410:Chemokine CCL7; D016207:Cytokines; D004311:Double-Blind Method; D006801:Humans; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000502:physiology*; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology
D000305:Adrenal Cortex Hormones; D000485:Allergens; C099677:CCL13 protein, human; C515450:CCL7 protein, human; D054410:Chemokine CCL7; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins