Regulation of the interleukin-5 receptor alpha-subunit on peripheral blood eosinophils from healthy subjects.
The aim was to study in vitro regulation of the IL-5 receptor alpha (IL-5R alpha) on purified peripheral blood eosinophils from healthy subjects. The IL-5R alpha was down-regulated, in a dose-dependent manner, by recombinant IL-5 and GM-CSF, with IL-5 being most potent. This down-regulation was not induced by autocrine release of GM-CSF or IL-5, respectively. Incubation of eosinophils with cell-free peritoneal dialysis fluid (PF) collected from a patient with peritoneal fluid eosinophilia (PFE), induced up-regulation of the proportion of CD69 positive eosinophils, in parallel with down-regulation of the proportion of IL-5R alpha positive eosinophils. Experiments with neutralizing antibodies against IL-5 and GM-CSF, revealed that IL-5 was the principal cytokine responsible for the down-regulation of the IL-5R alpha. When eosinophils were incubated with PF collected from the same patient in remission or with PF collected from a newly started patient or a patient with bacterial peritonitis, less down-regulation of the IL-5R alpha was observed. In conclusion our data indicate that IL-5, as opposed to its proposed action on eosinophil progenitors, down-regulates the IL-5R alpha chain on mature eosinophils. We therefore suggest that an IL-5 driven inflammation generates an eosinophil tissue phenotype that is characterized by a low IL-5R alpha expression. These aspects of IL-5 action on IL-5R alpha expression could gain new insights into the mechanisms of specific immuno-modulatory therapies, such as anti-IL-5.
Hellman
C
C
Department of Medicine, Division of Clinical Immunology and Allergy, Karolinska Institutet and Hospital, Stockholm, Sweden. Cecelia.Hellman@ks.se
Halldén
G
G
Hylander
B
B
Lundahl
J
J
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001202:Ascitic Fluid / Q000276:immunology; D002478:Cells, Cultured; D003864:Depression, Chemical; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D015848:Interleukin-5 / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D021122:Protein Subunits / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D021122:Protein Subunits; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor