1,1'-Ethylidenebis(tryptophan) (Peak E) induces functional activation of human eosinophils and interleukin 5 production from T lymphocytes: association of eosinophilia-myalgia syndrome with a L-tryptophan contaminant.
This study was designed to clarify the important association between eosinophilia-myalgia syndrome (EMS) and the L-tryptophan contaminant, "Peak E." To determine the functional activation of eosinophils induced by Peak E, eosinophil cationic protein (ECP) release was examined. Peak E augumented the release of ECP from peripheral blood normodense eosinophils by degranulation. Proliferative analysis using the human eosinophilic leukemia cell line EoL-3 showed prominent cellular replication in the presence of Peak E. Moreover, Peak E upregulated interleukin 5 (IL-5) receptor levels on normodense eosinophils. Of particular interest, Peak E-stimulated human splenic T cells produced bioactive and immunoreactive IL-5. Marked induction of IL-5 mRNA in Peak E-stimulated T cells was also shown by reverse-transcriptase polymerase chain reaction (RT-PCR). In contrast, L-tryptophan without the contaminant showed none of these effects. Thus, these data suggest that Peak E might be involved in the pathogenesis of EMS through bimodal mechanism including IL-5 generation by T cells and potentiation of eosinophil functional activation.
Yamaoka
K A
KA
U365-Institut National de la Santé et de la Recherche Médicale (INSERM), Interférons et Cytokines, Institut Curie, Paris, France.
Miyasaka
N
N
Inuo
G
G
Saito
I
I
Kolb
J P
JP
Fujita
K
K
Kashiwazaki
S
S
D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D001798:Blood Proteins / Q000096:biosynthesis; D004587:Electrophoresis, Agar Gel; D047091:Eosinophil Granule Proteins; D016603:Eosinophilia-Myalgia Syndrome / Q000209:etiology*; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053649:Receptors, Interleukin-5; D012260:Ribonucleases; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014364:Tryptophan / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology*; D014407:Tumor Cells, Cultured
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D015848:Interleukin-5; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; C070372:1,1'-ethylidene bis(tryptophan); D014364:Tryptophan; D012260:Ribonucleases