Modulation of eosinophil chemotaxis by interleukin-5.
Eosinophilia and eosinophil function are regulated by cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5). We have investigated the modulatory role of IL-5 on N-formyl-methionyl-leucyl-phenylalanine (FMLP), neutrophil-activating factor (NAF/IL-8), platelet factor 4 (PF4), and cytokine-induced chemotaxis of eosinophils from normal individuals. These eosinophils show a small chemotactic response toward PF4 but not to NAF/IL-8 and FMLP. Preincubation of eosinophils with low concentrations of IL-5 caused significantly increased responses toward PF4 and induced a significant chemotactic response toward FMLP and NAF/IL-8. In marked contrast, IL-5 (or IL-3) priming of eosinophils from normal donors resulted in a strong inhibition of GM-CSF-induced chemotaxis. A similar decrease in the chemotactic response toward GM-CSF was observed in eosinophils derived from allergic asthmatic individuals. This finding suggests that the latter eosinophils may have had a prior exposure to IL-5 (or IL-3). Washing of the cells after priming did not abrogate the inhibition of the GM-CSF response. Our data indicate that at low concentrations IL-5 is an important modulator of eosinophil chemotaxis, causing selective upregulation or downregulation of chemotactic responses toward different agents.
Warringa
R A
RA
Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
Schweizer
R C
RC
Maikoe
T
T
Kuijper
P H
PH
Bruijnzeel
P L
PL
Koendermann
L
L
D000328:Adult; D001249:Asthma / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004804:Eosinophils / Q000166:cytology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology*; D016209:Interleukin-8 / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D010978:Platelet Factor 4 / Q000502:physiology
D007377:Interleukin-3; D015848:Interleukin-5; D016209:Interleukin-8; D010978:Platelet Factor 4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor