Upregulation of formyl-peptide and interleukin-8-induced eosinophil chemotaxis in patients with allergic asthma.
BACKGROUND
The cytokine granulocyte-macrophage colony-stimulating factors, interleukin-3 and interleukin-5, are important modulators of eosinophilia and eosinophil function. In particular, eosinophil chemotaxis is very sensitive to cytokine priming.


METHODS
We evaluated chemotactic responses of eosinophils from patients with allergic asthma. These cells exhibited a primed phenotype as deduced from enhanced responses toward formyl-methionyl-leucyl-phenylalanine and platelet-activating factor and a decreased responsiveness toward granulocyte-macrophage colony-stimulating factor. Bronchoprovocation of patients with allergic asthma with allergen was performed as a possible means to enhance in vivo priming.


RESULTS
Indeed, eosinophils isolated 3 hours after allergen challenge exhibited a more pronounced primed phenotype, which was reflected by an induction of responsiveness towards interleukin-8. Eosinophil responses induced by platelet-activating factor, formyl-methionyl-leucyl-phenylalanine, complement fragment C5a, interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor were not significantly altered after allergen challenge.


CONCLUSIONS
These data provide further evidence that eosinophils are already primed in the peripheral blood of individuals with allergic asthma. This is most likely due to the presence of circulating cytokines in the peripheral blood of those individuals. This in vivo priming results in selective upregulation and downregulation of responses toward various chemotaxins, which may be released in the lungs during allergic inflammation.
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
R A
RA
Warringa
H J
HJ
Mengelers
J A
JA
Raaijmakers
P L
PL
Bruijnzeel
L
L
Koenderman
D000328:Adult; D001249:Asthma / Q000276:immunology*; D001985:Bronchial Provocation Tests; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015936:Complement C5a / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D015854:Up-Regulation
D016209:Interleukin-8; D010972:Platelet Activating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D016178:Granulocyte-Macrophage Colony-Stimulating Factor