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Expression and activity of NOX5 in the circulating malignant B cells of hairy cell leukemia.
J Immunol 2005; 175(12):8424-30JI

Abstract

Hairy cells (HCs) are mature malignant B cells that contain a number of constitutively active signaling molecules including GTP-bound Rac1, protein kinase C, and Src family kinases. Because Rac1 is a component of the reactive oxidant species (ROS)-generating NADPH oxidase system, we investigated the role of this GTPase in ROS production in HCs. In this study, we show that ROS production in HCs involves a flavin-containing oxidase dependent on Ca2+, but not on GTP-Rac1 or protein kinase C. This suggests the involvement of the nonphagocytic NADPH oxidase NOX5, an enzyme found in lymphoid tissues, but not in circulating lymphocytes. By using RT-PCR and Southern and Western blotting and by measuring superoxide anion production in membrane fractions in the absence of cytosolic components, we demonstrate for the first time that HCs (but not circulating normal B cells or some other lymphoid cell types) express NOX5. We also demonstrate that inhibition of NADPH oxidase in HCs results in a selective increase in the activity of Src homology region 2 domain-containing phosphatase 1 (SHP-1). Furthermore, SHP-1 in HCs coimmunoprecipitates with tyrosine phosphorylated CD22 and localizes in the same cellular compartment as NOX5. This allows the inactivation of SHP-1 by NOX5-generated ROS and contributes to the maintenance of the constitutive activation of HCs.

Authors+Show Affiliations

Department of Hematology, Royal Liverpool Hospital, University of Liverpool, Liverpool, United Kingdom. aurakami@liverpool.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16339585

Citation

Kamiguti, Aura S., et al. "Expression and Activity of NOX5 in the Circulating Malignant B Cells of Hairy Cell Leukemia." Journal of Immunology (Baltimore, Md. : 1950), vol. 175, no. 12, 2005, pp. 8424-30.
Kamiguti AS, Serrander L, Lin K, et al. Expression and activity of NOX5 in the circulating malignant B cells of hairy cell leukemia. J Immunol. 2005;175(12):8424-30.
Kamiguti, A. S., Serrander, L., Lin, K., Harris, R. J., Cawley, J. C., Allsup, D. J., ... Zuzel, M. (2005). Expression and activity of NOX5 in the circulating malignant B cells of hairy cell leukemia. Journal of Immunology (Baltimore, Md. : 1950), 175(12), pp. 8424-30.
Kamiguti AS, et al. Expression and Activity of NOX5 in the Circulating Malignant B Cells of Hairy Cell Leukemia. J Immunol. 2005 Dec 15;175(12):8424-30. PubMed PMID: 16339585.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression and activity of NOX5 in the circulating malignant B cells of hairy cell leukemia. AU - Kamiguti,Aura S, AU - Serrander,Lena, AU - Lin,Ke, AU - Harris,Robert J, AU - Cawley,John C, AU - Allsup,David J, AU - Slupsky,Joseph R, AU - Krause,Karl-Heinz, AU - Zuzel,Mirko, PY - 2005/12/13/pubmed PY - 2006/3/23/medline PY - 2005/12/13/entrez SP - 8424 EP - 30 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 175 IS - 12 N2 - Hairy cells (HCs) are mature malignant B cells that contain a number of constitutively active signaling molecules including GTP-bound Rac1, protein kinase C, and Src family kinases. Because Rac1 is a component of the reactive oxidant species (ROS)-generating NADPH oxidase system, we investigated the role of this GTPase in ROS production in HCs. In this study, we show that ROS production in HCs involves a flavin-containing oxidase dependent on Ca2+, but not on GTP-Rac1 or protein kinase C. This suggests the involvement of the nonphagocytic NADPH oxidase NOX5, an enzyme found in lymphoid tissues, but not in circulating lymphocytes. By using RT-PCR and Southern and Western blotting and by measuring superoxide anion production in membrane fractions in the absence of cytosolic components, we demonstrate for the first time that HCs (but not circulating normal B cells or some other lymphoid cell types) express NOX5. We also demonstrate that inhibition of NADPH oxidase in HCs results in a selective increase in the activity of Src homology region 2 domain-containing phosphatase 1 (SHP-1). Furthermore, SHP-1 in HCs coimmunoprecipitates with tyrosine phosphorylated CD22 and localizes in the same cellular compartment as NOX5. This allows the inactivation of SHP-1 by NOX5-generated ROS and contributes to the maintenance of the constitutive activation of HCs. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/16339585/Expression_and_activity_of_NOX5_in_the_circulating_malignant_B_cells_of_hairy_cell_leukemia_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16339585 DB - PRIME DP - Unbound Medicine ER -