PD-1 Regulates the Growth of Human Mastocytosis Cells

• Published in: Allergology International Vol. 62; no. 1; pp. 99 - 104
• Main Authors: Kataoka, Tatsuki R, Fujimoto, Masakazu, Moriyoshi, Koki, Koyanagi, Itsuko, Ueshima, Chiyuki, Kono, Fumihiko, Tsuruyama, Tatsuaki, Okayama, Yoshimichi, Ra, Chisei, Haga, Hironori
• Format: Journal Article
• Language: Japanese; English
• Published: England JAPANESE SOCIETY OF ALLERGOLOGY 2013; Elsevier
• Subjects: Cell Line; Cell Proliferation - drug effects; Gene Expression; Humans; inhibitory receptor; mast cell; mastocytosis; Mastocytosis, Cutaneous - genetics; Mastocytosis, Cutaneous - metabolism; PD-1; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacology
• ISSN: 1323-8930; 1440-1592
• DOI: 10.2332/allergolint.12-oa-0450

[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 RTPCR, 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.