In vivo priming of platelet-activating factor-induced eosinophil chemotaxis in allergic asthmatic individuals.
The cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 are important modulators of eosinophilia and eosinophil function. Eosinophil chemotaxis is known to be particularly sensitive for cytokine priming. In the present study, we compared chemotactic responses of eosinophils derived from peripheral blood of allergic asthmatics to responses of eosinophils from peripheral blood of healthy individuals. Eosinophils from allergic asthmatics exhibited a markedly increased sensitivity in their chemotactic response toward platelet-activating factor (PAF) compared with eosinophils from normal donors. In contrast, C5a-induced eosinophil chemotaxis between both groups was similar. This in vivo-primed phenotype could be mimicked in vitro, by preincubating eosinophils from peripheral blood of healthy individuals with picomolar concentrations of either GM-CSF, IL-3, or IL-5. The chemotactic response of eosinophils derived from the circulation of allergic asthmatic patients toward GM-CSF was significantly lower compared with the response of eosinophils of healthy individuals. Our data strongly suggest that release of cytokines may be an important in vivo priming mechanism for eosinophils in the circulation of allergic asthmatic patients. Such an in vivo priming can subsequently result in selective upregulation and downregulation of chemotactic responses toward various chemoattractants release in the lung tissue.
Warringa
R A
RA
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
Mengelers
H J
HJ
Kuijper
P H
PH
Raaijmakers
J A
JA
Bruijnzeel
P L
PL
Koenderman
L
L
D001249:Asthma / Q000473:pathology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D015936:Complement C5a / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004804:Eosinophils / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*
D016207:Cytokines; D007377:Interleukin-3; D015848:Interleukin-5; D010972:Platelet Activating Factor; D015936:Complement C5a; D016178:Granulocyte-Macrophage Colony-Stimulating Factor