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Modulation and induction of eosinophil chemotaxis by granulocyte-
macrophage colony-stimulating factor and interleukin-3
RA Warringa, L Koenderman, PT Kok, J Kreukniet and PL Bruijnzeel
Department of Pulmonary Diseases, University Hospital Utrecht, The
Netherlands.
Eosinophilia and eosinophil function are regulated by cytokines such as
granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin- 3
(IL-3), and IL-5. We have investigated the modulatory role of GM-CSF and
IL-3 on the platelet-activating factor (PAF)-, neutrophil- activating
factor (NAF/IL-8)-, leukotriene B4 (LTB4)-, N-formyl-
methionyl-leucyl-phenylalanine (FMLP)-, and human complement factor C5a-
induced chemotaxis of eosinophils from normal individuals. These
eosinophils show a chemotactic response toward PAF, LTB4, and C5a, but not
to NAF/IL-8 and FMLP. Preincubation of the eosinophils with picomolar
concentrations of GM-CSF caused a significant increase in the response
toward LTB4 and induced a significant chemotactic response toward NAF/IL-8
and FMLP. Preincubation of the eosinophils with picomolar concentrations of
IL-3 also induced a chemotactic response toward NAF/IL-8 and FMLP, and
enhanced the PAF-induced chemotaxis response toward C5a was not influenced
by both cytokines. Nanomolar concentrations of GM-CSF or IL-3 caused a
significant inhibition of the C5a-induced chemotaxis. The LTB4-induced
chemotaxis was also significantly inhibited in case of GM-CSF. At these
concentrations both GM-CSF and IL-3 acted as chemotaxins for eosinophils
were washed after pretreatment with GM-CSF and IL-3 the potentiation of the
chemotactic response remained, whereas the inhibitory mode of action
disappeared. Our data indicate that at picomolar concentrations the
cytokines GM-CSF and IL-3 can modulate eosinophil chemotaxis and at
nanomolar concentrations these cytokines can act as chemotaxins for
eosinophils.
Volume 77,
Issue 12,
pp. 2694-2700,
06/15/1991
Copyright © 1991 by The American Society of Hematology
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