title: Chemokine system and tissue infiltration in aggressive NK-cell leukemia.
abstract: NK cell-type lymphoproliferative disease of granular lymphocytes can be subdivided into aggressive NK-cell leukemia (ANKL) and chronic NK-cell lymphocytosis (CNKL). Hepatosplenomegaly is observed in ANKL patients, and hepatic failure is a common cause of death. Significant numbers of ANKL cells were pathologically observed in sinusoidal and interlobular regions of the liver, and in the splenic red pulp. In our previous study, ANKL cells were simultaneously positive for CXCR1 and CCR5. So, in order to elucidate the mechanism in the systemic migration of ANKL cells, we investigated the expression of the corresponding chemokines in ANKL compared with CNKL. The serum level of IL-8, MIP-1alpha and MIP-1beta was significantly elevated in ANKL patients, and ANKL cells were highly positive for IL-8, RANTES, MIP-1alpha and MIP-1beta according to intracellular staining and RT-PCR. These chemokines were also positively stained in hepatocytes. The interaction between Fas and Fas ligand (FasL) is supposed to be one of the mechanisms for liver dysfunction in ANKL. The serum concentration of soluble FasL was significantly high in ANKL patients, and ANKL cells expressed FasL protein in the cytoplasm. These results suggest that the chemokine system plays an important role in the transmigration of FasL-expressing ANKL cells.
authors.affiliation: Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.forename: Toshiro
authors.initials: T
authors.lastname: Ito
authors.forename: Kayoko
authors.initials: K
authors.lastname: Momose
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Shimodaira
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kamijo
authors.forename: Yozo
authors.initials: Y
authors.lastname: Nakazawa
authors.forename: Naoaki
authors.initials: N
authors.lastname: Ichikawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ueno
authors.forename: Hikaru
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kitano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Kendo
authors.initials: K
authors.lastname: Kiyosawa
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Ishida
mesh_terms: D018925:Chemokines / Q000097:blood* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007694:Killer Cells, Natural / Q000473:pathology*; D007945:Leukemia, Lymphoid / Q000097:blood* / Q000235:genetics; D008218:Lymphocytosis / Q000097:blood*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018925:Chemokines; D053222:Fas Ligand Protein; D012333:RNA, Messenger; D012334:RNA, Neoplasm