title: Peripheral blood CD56(bright) NK cells respond to stem cell factor and adhere to its membrane-bound form after upregulation of c-kit.
abstract: CD56(bright) NK cells express receptors for IL-2, IL-7, IL-15, and SCF. We found that human peripheral blood CD56(bright) NK cells responded to IL-2, IL-7, IL-15 by phosphorylating STAT-5, ERK, and Akt but did not respond to SCF. However, CD56(bright) NK cells in culture upregulated c-kit transcription three to fourfold, which led to a steady increase in c-kit and a concomitant acquisition of responsiveness to SCF. After 44 h, CD56(bright) NK cells had upregulated c-kit approximately 20-fold and phosphorylated ERK and Akt in response to SCF concentrations well below levels present in plasma. CD56(bright) NK cells cultured in IL-15 maintained c-kit transcription/expression at ex vivo levels and did not become responsive to SCF. Furthermore, SCF-responsive, CD56(bright) c-kit(high) NK cells swiftly downregulated c-kit and stopped responding to SCF after IL-15 stimulation. However, commitment of CD56(bright) NK cells to a c-kit-negative, SCF-unresponsive state did not occur, as after 5 days of culture, withdrawal of IL-15 restored c-kit to maximal levels and reestablished SCF-responsiveness. CD56(bright) NK cells that had upregulated c-kit firmly adhered to COS cells transfected with the membrane form of SCF. Furthermore, SCF signaling significantly increased the capacity of CD56(bright) NK cells to degranulate. Collectively, our data suggest that c-kit on human CD56(bright) NK cells is a functional receptor that is downregulated in peripheral blood, possibly to render CD56(bright) NK cells unresponsive to the SCF therein.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Geneva University Hospitals and University of Geneva, Switzerland.
authors.forename: Amandine
authors.initials: A
authors.lastname: Pradier
authors.forename: Severine
authors.initials: S
authors.lastname: Tabone-Eglinger
authors.forename: Vincent
authors.initials: V
authors.lastname: Huber
authors.forename: Carine
authors.initials: C
authors.lastname: Bosshard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Rigal
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wehrle-Haller
authors.forename: Eddy
authors.initials: E
authors.lastname: Roosnek
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015536:Down-Regulation / Q000235:genetics; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D019002:CD56 Antigen; D019409:Interleukin-15; C522918:NCAM1 protein, human; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt
keywords: Cytokines; Human; Inflammation; NK cells; SCF; c-Kit