Interleukin-8 and RANTES induce the adhesion of the human basophilic cell line KU-812 to human endothelial cell monolayers.
Basophils are implicated in the pathogenesis of the late-phase allergic reaction, but the mechanisms by which circulating basophils adhere to vascular endothelium and migrate to lesional sites remain unclear. In order to assess the biological similarity of the basophilic cell line KU-812 to normal human basophils, we have compared the adhesion response of this cell line and normal basophils, following challenge with interleukin-8 (IL-8) and RANTES. We demonstrate here that IL-8 and RANTES are able to stimulate the adherence of the basophilic cell line, KU-812, to cytokine-activated human umbilical vein endothelium (HUVEC). The chemokine-induced increase in adhesion was dose-related and was maximal after prior priming with IL-5. The stimulation of adhesion was partially inhibited by co-incubation with anti-CD18 and anti-CD11c antibodies and antibodies to the beta 1-integrins. In comparison, the chemokine-induced adhesion of normal human basophils was only inhibited by the beta 2-integrins. These chemokines were also able to induce the migration of KU-812 in a dose-dependent manner, but only after prior treatment with phorbol myristate acetate (PMA) or IL-5. In all cases tested, IL-8 was more potent and efficacious than RANTES. We conclude from these studies that these members of the chemokine superfamily may play an important role in the recruitment of reactive leukocytes in allergic inflammation, by stimulating their adhesion and subsequent migration from the vasculature into the inflammatory sites. However, it is apparent that KU-812 is not an adequate substitute for normal human basophils in order to investigate chemokine biology.
Bacon
K B
KB
Glaxo Institute for Molecular Biology, Geneva, Switzerland.
Flores-Romo
L
L
Aubry
J P
JP
Wells
T N
TN
Power
C A
CA
D001483:Base Sequence; D001491:Basophils / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002460:Cell Line; D018946:Chemokine CCL5; D002634:Chemotaxis, Leukocyte; D004306:Dose-Response Relationship, Immunologic; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D015848:Interleukin-5 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology*; D008222:Lymphokines / Q000276:immunology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015815:Cell Adhesion Molecules; D018946:Chemokine CCL5; D015848:Interleukin-5; D016209:Interleukin-8; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium