title: Granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 greatly enhance the interaction of human eosinophils with opsonized particles by changing the affinity of complement receptor type 3.
abstract: Eosinophil functions can be modulated by several cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5. We have investigated the modulatory role of these cytokines on the interaction of human eosinophils with opsonized particles (serum-treated zymosan [STZ]). Addition of STZ to eosinophils isolated from the peripheral blood of normal human donors resulted in an interaction of the STZ particles with only 15% to 25% of the cells. Treatment of the eosinophils with GM-CSF, IL-3, or IL-5 strongly enhanced both the rate of particle binding and the percentage of eosinophils binding STZ. The effect of the cytokines is most likely mediated by a change in affinity of the complement receptor type 3 (CR3) on the eosinophils for the complement fragment iC3b on the STZ particles. This is indicated by the observation that (1) the effect of the cytokines on STZ binding was prevented by a monoclonal antibody against the iC3b-binding site on CR3 and (2) the enhanced binding was already apparent before upregulation of CR3 on the cell surface was observed. In a previous study, similar results were obtained with platelet-activating factor (PAF)-primed eosinophils. Because we found that the cytokines strongly enhanced the STZ-induced PAF synthesis, we investigated the role of both released PAF and cell-associated PAF in the priming phenomenon by the cytokines. Cytokine priming appeared to be largely independent of the synthesis of PAF.
authors.affiliation: Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Blom
authors.forename: A T
authors.initials: AT
authors.lastname: Tool
authors.forename: P T
authors.initials: PT
authors.lastname: Kok
authors.forename: L
authors.initials: L
authors.lastname: Koenderman
authors.forename: D
authors.initials: D
authors.lastname: Roos
authors.forename: A J
authors.initials: AJ
authors.lastname: Verhoeven
mesh_terms: D004804:Eosinophils / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis; D010972:Platelet Activating Factor / Q000096:biosynthesis; D011796:Quinacrine / Q000494:pharmacology; D015054:Zymosan / Q000378:metabolism
chemical_list: D007377:Interleukin-3; D015848:Interleukin-5; D016177:Macrophage-1 Antigen; D010972:Platelet Activating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015054:Zymosan; D011796:Quinacrine