Enhancement by stem cell factor of interleukin-2 (IL-2)-induced DNA synthesis in human decidual CD16- CD56bright natural killer cells mediated by increased expression of the IL-2 receptor alpha chain.
Extracts of chorionic villous and decidual tissue specimens from women in the early stages of pregnancy contained stem cell factor (SCF), the amount in the latter tissue (246.6+/-119.7 pg/mg protein) being approximately three times that in the former. Immunohistochemical analysis revealed the presence of SCF in the mesenchymal cells of the chorion, the trophoblast, and decidual stromal cells, whereas the SCF receptor, c-kit, was detected in the trophoblast and decidual mononuclear leukocytes but not in decidual stromal cells. Reverse transcription and polymerase chain reaction analysis detected transcripts corresponding to both secretory and membrane-bound types of SCF in chorionic tissue, but only those encoding the secretory type in decidual tissue. Flow cytometric analysis showed that c-kit was expressed on decidual CD16- CD56bright natural killer (NK) cells, CD14+ macrophages, and CD34+ hematopoietic progenitor cells, but not on CD3+ T cells or CD16+ NK cells. Although SCF alone had no effect on DNA synthesis in decidual CD16- CD56bright NK cells, it enhanced the proliferative effect of interleukin-2 (IL-2) at IL-2 concentrations that selectively saturate the high-affinity IL-2 receptor (IL-2R). Flow cytometry of decidual mononuclear leukocytes cultured in the presence of SCF demonstrated that this factor increased the expression of the IL-2Ralpha chain, but not IL-2Rbeta and gamma chain expression on CD16- CD56bright NK cells. Results suggest that SCF produced in the decidua increases the expression of the IL-2Ralpha which is usually present in smaller amounts than other two IL-2R chains on decidual CD16- CD56bright NK cells, and thereby promotes the proliferation of these cells in response to low concentrations of IL-2, resulting in an increase of the high affinity IL-2Rs.
Umekage
H
H
Department of Obstetrics and Gynecology, Nara Medical University, Kashihara-shi, Japan.
Saito
S
S
Morikawa
H
H
D019002:CD56 Antigen; D002824:Chorionic Villi / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000096:biosynthesis*; D003656:Decidua / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005312:Fetal Blood; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*
D019002:CD56 Antigen; D007376:Interleukin-2; D012333:RNA, Messenger; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2; D019089:Stem Cell Factor; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit