title: PD-1 regulates the growth of human mastocytosis cells.
abstract: BACKGROUND
  Programmed death-1 (PD-1) is a marker for human neoplastic T cells. Here, we evaluated whether or not PD-1 was also a marker for human mastocytosis, and explored the role of PD-1 in human mastocytosis cells.
  
  
  METHODS
  Immunohistochemical analysis was used to evaluate the expression of PD-1 in clinical samples of human cutaneous mastocytosis. The expression of PD-1 in human mastocytosis cell lines was checked by RT-PCR, western blotting and flow cytometry. We stimulated human mastocytosis cell lines (LAD2 and HMC1.2) with recombinant ligand for PD-1, PD-L1 (rPD-L1), and tested the proliferative activity and the status of signal molecules by Cell Counting Kit-8 and ELISA, respectively.
  
  
  RESULTS
  Ten of 30 human cutaneous mastocytosis cases (33.3%) expressed PD-1 protein. We also found that a human mastocytosis line LAD2 cells expressed PD-1 protein on their surfaces. The administration with rPD-L1 suppressed the stem cell factor-dependent growth of the LAD2 cells. And, rPD-L1 activated SHP-1 and SHP-2 simultaneously, and decreased the phosphorylation of AKT, in LAD2 cells. In contrast, we could not detect the expression of PD-1, and the significant effect of rPD-L1 on the mutated KIT-driven growth of HMC1.2 cells.
  
  
  CONCLUSIONS
  PD-1 could be a marker for human cutaneous mastocytosis and regulate the growth of human PD-1-positive mastocytosis cells.
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. trkataoka@yahoo.co.jp
authors.forename: Tatsuki R
authors.initials: TR
authors.lastname: Kataoka
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Koki
authors.initials: K
authors.lastname: Moriyoshi
authors.forename: Itsuko
authors.initials: I
authors.lastname: Koyanagi
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Ueshima
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kono
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Okayama
authors.forename: Chisei
authors.initials: C
authors.lastname: Ra
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D034701:Mastocytosis, Cutaneous / Q000235:genetics / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011994:Recombinant Proteins