Effect of L-tryptophan products on function of human eosinophils: investigation of the causal mechanisms of eosinophilia myalgia syndrome associated with L-tryptophan products.
Contaminants in the L-tryptophan products, known as peak-E and peak-5, at a concentration of 1-10 micrograms/ml had the ability to elicit chemokinetic migration of eosinophils. Purified eosinophils adhered to peak-E- or peak-5-stimulated human umbilical vein endothelial cells, and this adherence was inhibited by the presence of antibody to intercellular adhesion molecule-1, but not by vascular cell adhesion molecule-1 antibody. Neither contaminant affected the expression of integrins, e.g. CD11b or CD49d, on the purified eosinophils. Human peripheral blood mononuclear cells (PBMCs) produced eosinophil survival-enhancing activity when cultivated with peak-E, but not with medium alone, peak-5 or control tryptophan. This activity of peak-E was significantly inhibited (p < 0.01) by the presence of antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition, expression of GM-CSF mRNA was found in total cellular RNA isolated from peak-E-stimulated PBMCs. Eosinophils acquired the ability to migrate toward interleukin-8 (IL-8) when preincubated with the contaminants of interest. IL-8 also bound to the contaminant-stimulated eosinophils, but not to those stimulated with medium alone. These findings suggest that contaminants in the L-tryptophan products modify the several functions of eosinophils and play a role in the pathogenesis of eosinophil myalgia syndrome.
Saito
H
H
Clinical Research Center for Rheumato-Allergology, National Sagamihara Hospital, Kanagawa, Japan.
Miyamoto
T
T
D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016603:Eosinophilia-Myalgia Syndrome / Q000209:etiology*; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D016209:Interleukin-8; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014364:Tryptophan