Eosinophil migration in atopic dermatitis. I: Increased migratory responses to N-formyl-methionyl-leucyl-phenylalanine, neutrophil-activating factor, platelet-activating factor, and platelet factor 4.
Eosinophil granular protein deposits have been demonstrated in lesional atopic dermatitis skin. This suggests active tissue infiltration of eosinophils. To find an explanation for the tissue influx of eosinophils, eosinophil migration was studied in vitro by means of a microchemotaxis assay. Eosinophils from the circulation of patients with atopic dermatitis showed an altered capacity to respond to chemotactic stimuli in vitro compared with eosinophils from healthy donors. Eosinophils from patients with atopic dermatitis had significantly increased migratory responses toward dose ranges of N-formyl-methionyl-leucyl-phenylalanine, neutrophil-activating factor, platelet-activating factor, and platelet factor 4. Eosinophils from normal individuals did not respond to N-formyl-methionyl-leucyl-phenylalanine and neutrophil-activating factor and responded only slightly to platelet factor 4. The migratory responses toward tumor necrosis factor-alpha and complement factor C5a were identical in both groups. Interleukin-5, an eosinophil-selective cytokine, is a strong modulator of the migratory responses to these chemotaxins in eosinophils from normal donors. A migratory response toward N-formyl-methionyl-leucyl-phenylalanine and neutrophil-activating factor was induced by interleukin-5, whereas the migratory response toward platelet-activating factor and platelet factor 4 was markedly potentiated. In contrast, the response to complement fragment C5a was only slightly influenced. Our findings indicate that the increased migratory responsiveness of eosinophils from patients with atopic dermatitis to various chemotaxins reflects in vivo "priming" of eosinophils, presumably by circulating cytokines such as interleukin-5. This in vivo "priming" is not optimal because it can be further potentiated by renewed contact with interleukin-5.
Bruijnzeel
P L
PL
Swiss Institute of Allergy and Asthma Research, Davos-Platz.
Kuijper
P H
PH
Rihs
S
S
Betz
S
S
Warringa
R A
RA
Koenderman
L
L
D000293:Adolescent; D000328:Adult; D002465:Cell Movement / Q000187:drug effects*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D015936:Complement C5a / Q000494:pharmacology; D003876:Dermatitis, Atopic / Q000097:blood* / Q000503:physiopathology*; D004804:Eosinophils / Q000502:physiology; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010978:Platelet Factor 4 / Q000494:pharmacology*
D015848:Interleukin-5; D016209:Interleukin-8; D010972:Platelet Activating Factor; D010978:Platelet Factor 4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a