title: Triphenyltin enhances the neutrophilic differentiation of promyelocytic HL-60 cells.
abstract: Triphenyltin (TPT) is an environmental endocrine disruptor and toxic substance, but little information is available on its immunological effects. To assess the effect of TPT on leukocyte differentiation, we investigated its effect on the neutrophilic differentiation of HL-60 cells induced by dimethyl sulfoxide and granulocyte colony-stimulating factor (G-CSF) for 6 days. At a low concentration, 10(-7)M, TPT increased superoxide production by differentiated HL-60 cells stimulated with opsonized zymosan (OZ) by about 45% and increased expression of CD18, a component of the OZ-receptor, by about 90%. Real-time PCR analysis revealed that TPT augmented the expression not only of CD18 but also of components of superoxide-generating NADPH-oxidase, p47phox, 2.7-fold, and p67phox, 2.0-fold, and of granulocyte colony-stimulating factor receptor (G-CSFR), 3.0-fold, whereas various other endocrine disruptors, including parathion, vinclozolin, and bisphenol A, had no such enhancing effects. The results of a DNA macroarray analysis showed that TPT enhanced the expression of G-CSFR and certain other neutrophil functional proteins, including CD14 and myeloid leukemia cell differentiation protein (MCL-1), and that TPT induced a decrease in expression of LC-PTP, leukocyte protein-tyrosine phosphatase, to about half the control level. The TPT-dependent suppression of LC-PTP was confirmed by real-time PCR analysis, and the results of immunoblotting indicated that TPT enhances the expression of myeloid specific tyrosine kinase hck by about 30% at the protein level, and this together with the reduction of LC-PTP may enhance tyrosine phosphorylation, in turn resulting in enhancement of superoxide production. These findings suggest that TPT may have an enhancing effect on the neutrophilic maturation of leukocytes.
authors.affiliation: National Institute of Health Sciences, 18-1 Kamiyoga 1-chome, Setagaya-ku, 158-8501, Tokyo, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Reiko
authors.initials: R
authors.lastname: Adachi
authors.forename: Akiko
authors.initials: A
authors.lastname: Hirayama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D019255:NADPH Oxidases / Q000235:genetics; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009947:Organotin Compounds / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051572:Proto-Oncogene Proteins c-hck; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics; D013481:Superoxides / Q000378:metabolism
chemical_list: D018821:CD18 Antigens; D004785:Environmental Pollutants; D009947:Organotin Compounds; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016188:Receptors, Granulocyte Colony-Stimulating Factor; C079789:neutrophil cytosol factor 67K; D013481:Superoxides; C030665:triphenyltin; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D011505:Protein-Tyrosine Kinases; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck