The role of the Duffy antigen-related chemokine receptor in psoriasis vulgaris.
Chemokines represent a family of potent biological mediators. Within the group of receptors mediating their effects, a promiscuous receptor has been found which is able to bind and inactivate diverse chemokines of both C-C and C-X-C families. It is co-localized with blood group antigens of the Duffy system on the same glycoprotein and expressed on red blood cells as well as post-capillary blood vessels. In the present study three aspects of Duffy pathophysiology were studied: firstly the amount of IL-8 and RANTES binding to red blood cells and its correlation to disease activity of psoriatic patients, secondly the distribution of Duffy phenotype among psoriatic patients and thirdly the expression of Duffy antigen in normal vs psoriatic skin. Red blood cells from psoriatic patients (n=50) were lysed by triton X (1%) and supernatants tested in IL-8- and RANTES sandwich-ELISA. Duffy phenotype of psoriatic patients (n=50) was assessed by typing red blood cells with specific antisera in indirect Coombs technique. For immunohistochemical detection in normal and psoriatic skin (n=10 respectively) a specific monoclonal antibody (Fy6) was used. Neither IL-8- nor RANTES-levels on red blood cells correlated to disease activity and distribution of Duffy phenotype in psoriatics was not significantly altered when compared to the normal population. Furthermore, Duffy antigen was expressed in a similar pattern in normal and psoriatic skin at all parts of vasculature, albeit much more abundantly in diseased skin. Altogether, chemokine binding to red blood cells seems of minor importance in psoriasis. However, Duffy antigen together with other binding mechanisms like proteoglycans may play a role at local level by binding locally produced chemokines. Thus biological effects of chemokines are both restricted and focussed to dermal tissue.
Sticherling
Michael
M
Department of Dermatology, Clinical Research Group, University of Kiel, Schittenhelmstr. 7, Germany. sticm@medizin.uni-leipzig.de
Baisch
Claudia
C
Bornscheuer
Erika
E
Schröder
Jens-M
JM
Christophers
Enno
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018946:Chemokine CCL5 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004375:Duffy Blood-Group System / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011565:Psoriasis / Q000378:metabolism*; D012867:Skin / Q000473:pathology*
D018946:Chemokine CCL5; D004375:Duffy Blood-Group System; D016209:Interleukin-8