Activation of human eosinophils and differentiated HL-60 cells by interleukin-5.
The ability of recombinant human interleukin-5 (rhIL-5) to bind to human eosinophils (HEOS), and to eosinophil-like erythroleukemic cells (butyric acid differentiated HL-60 cells), and also to prime the phorbol myristate acetate ester (PMA)-induced respiratory burst of these cells was assessed. Both cell types expressed a high affinity (KD approximately 19 pM as measured ar 37 degrees C) IL-5 receptor and could be significantly primed by short (1 h) preincubation with 1 nM rhIL-5 as shown by leftward shifts of the PMA dose-response curves, and increased maximal responses (PMA EC50 without IL-5, 0.85 +/- 0.14 nM; with 1 nM IL-5, 0.47 +/- 0.15 nM, n = 6 donors; p < 0.05). In HL-60 cells, priming was dose-dependent, with an EC50 of 17 +/- 11 pM, and could be neutralised by an anti-interleukin-5 antibody (IC50 approximately 10 nM for the priming effect of 1 nM rhIL-5). A longer (24 h) incubation of HEOS with IL-5 appeared to potentiate the effect of the cytokine, which was greatest in cells from subjects with modest eosinophilia. These data suggest that interleukin-5 is a potent and rapidly acting priming agent for eosinophils, and that release of IL-5 during an allergic asthmatic reaction may contribute to the observed activation of these granulocytes.
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Dorval, Canada.
P
P
Tagari
E I
EI
Pecheur
M
M
Scheid
P
P
Brown
A W
AW
Ford-Hutchinson
D
D
Nicholson
D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D007942:Leukemia, Experimental; D011971:Receptors, Immunologic / Q000032:analysis; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D011994:Recombinant Proteins / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000648:ultrastructure
D002087:Butyrates; D015848:Interleukin-5; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D011994:Recombinant Proteins; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate