title: Up-regulation of CCL11 and CCL26 is associated with activated eosinophils in bullous pemphigoid.
abstract: Eosinophils contribute to the pathogenesis of bullous pemphigoid (BP) by secretion of proinflammatory cytokines and proteases. Trafficking of eosinophils into tissue in animal models and asthma depends on interleukin-5 and a family of chemokines named eotaxins, comprising CCL11, CCL24 and CCL26. Up-regulation of CCL11 has been described in BP, but the expression of the other two members of the eotaxin-family, CCL24 and CCL26, has not been investigated. In addition to these chemokines, expression of adhesion molecules associated with eosinophil migration to the skin should be analysed. We demonstrate that similar to CCL11, the concentration of CCL26 was up-regulated in serum and blister fluid of BP patients. In contrast, the concentration of CCL24 was not elevated in sera and blister fluid of the same BP patients. In lesional skin, CCL11 and CCL26 were detected in epidermis and dermis by immunohistochemistry. In contrast to CCL11, CCL26 was expressed strongly by endothelial cells. In line with these findings, eosinophils represented the dominating cell population in BP lesional skin outnumbering other leucocytes. The percentage of eosinophils expressing very late antigen (VLA): VLA-4 (CD49d) and CD11c correlated with their quantity in tissue. Macrophage antigen (MAC)-1 (CD11b/CD18) was expressed constitutively by tissue eosinophils. In conclusion, these data link the up-regulation of the eosinophil chemotactic factor CCL26 in BP to the lesional accumulation of activated eosinophils in the skin. Thereby they broaden the understanding of BP pathogenesis and might indicate new options for therapeutic intervention.
authors: University Hospital for Dermatology, Technical University Dresden, Dresden, Germany. claudia.guenther@uniklinikum-dresden.de
authors: C
authors: C
authors: Günther
authors: G
authors: G
authors: Wozel
authors: M
authors: M
authors: Meurer
authors: C
authors: C
authors: Pfeiffer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001768:Blister / Q000276:immunology; D039521:CD11c Antigen / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis; D054413:Chemokine CCL11 / Q000097:blood*; D054423:Chemokine CCL24 / Q000097:blood; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000097:blood*; D002631:Chemotactic Factors, Eosinophil / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D039041:Integrin alpha4beta1 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010391:Pemphigoid, Bullous / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology
chemical_list: C515456:CCL11 protein, human; C515484:CCL24 protein, human; C120429:CCL26 protein, human; D039521:CD11c Antigen; D018821:CD18 Antigens; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D039041:Integrin alpha4beta1; D016177:Macrophage-1 Antigen