Increased expression of Th2-associated chemokines in bullous pemphigoid disease. Role of eosinophils in the production and release of these chemokines.
Bullous pemphigoid is an inflammatory disease of the skin associated with eosinophil infiltration and the presence of high levels of Th2 cytokines in the associated blister fluid. Little is known about the contribution of chemokines in this disease. We found that eotaxin and MCP-4 mRNA and immunoreactivity were expressed in all biopsies of BP patients and were mainly localized to the epidermis and eosinophils. The expression of eotaxin and MCP-4 was enhanced in eosinophils following IL-5 treatment. Subsequent stimulation of IL-5-primed eosinophils with Ig-immune complexes, results in increase secretion of eotaxin and MCP-4 in the supernatants. Using immunostaining, these two chemokines were localized to the granules of eosinophils. BF was found to contain chemotactic activity for eosinophils, neutrophils and T cells. The chemotactic effect of BF for eosinophils was more effective when eosinophils were stimulated with IL-5 or IL-4. We also found that the levels of Th(2)-associated chemokines (eotaxin and MCP-4) in BF were significantly higher than the Th(1)-associated chemokines (MIP-1beta and IP-10). This was consistent with the increased chemotaxis of polarized Th(2) cells toward BF, when compared to Th(1)-differentiated T cells. Our results support the involvement of Th(2)-associated chemokines in the pathogenesis of BP disease.
Gounni Abdelilah
Soussi
S
Department of Immunology, University of Manitoba, 603A BSMB, 730 William Avenue, Winnipeg, Manitoba, Canada R3E 0W3.
Wellemans
Vincent
V
Agouli
Mourad
M
Guenounou
Moncef
M
Hamid
Qutayba
Q
Beck
Lisa A
LA
Lamkhioued
Bouchaib
B
D000328:Adult; D001768:Blister / Q000276:immunology; D054413:Chemokine CCL11; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D010391:Pemphigoid, Bullous / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018418:Th2 Cells / Q000276:immunology*
C515456:CCL11 protein, human; C099677:CCL13 protein, human; D054413:Chemokine CCL11; D018925:Chemokines; D019742:Chemokines, CC; D015848:Interleukin-5; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D015847:Interleukin-4