Expression of c-kit and kit ligand at the human maternofetal interface.
Kit ligand, or stem cell factor, is a recently identified growth factor, which binds to and activates the c-kit proto-oncogene, and which has been shown to act synergistically with other haematopoietic growth factors in the bone marrow. We have previously shown that several isoforms of kit ligand, which arise due to alternative splicing, are expressed in human placenta. In order to elucidate the role of c-kit and its ligand during human placental development we have investigated the expression of c-kit and kit ligand in human first trimester and term placenta as well as in pregnant and non-pregnant endometrium, by immunocytochemistry and flow cytometric analysis. In non-pregnant endometrium no expression of kit ligand was seen. By contrast, in first trimester decidua, kit ligand was strongly expressed by the arterial media of maternal blood vessels. Kit ligand was also expressed throughout pregnancy by invasive fetal extravillous trophoblast, and by fetal fibroblasts within the placental villi. c-kit was found to be expressed on Hofbauer cells within the chorionic villi, and by decidual macrophages at all stages in pregnancy. c-kit was also detected on the small CD56dim subset of uterine large granular lymphocytes which form the major leukocyte population in human first trimester decidua. Our results suggest that kit ligand may be involved in the regulation of fetal macrophages, and in particular in signalling between invading extravillous trophoblast which expresses kit ligand, and maternal leukocytes bearing the c-kit receptor.
Sharkey
A M
AM
Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Maternity Hospital, UK.
Jokhi
P P
PP
King
A
A
Loke
Y W
YW
Brown
K D
KD
Smith
S K
SK
D000595:Amino Acid Sequence; D000650:Amnion / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002823:Chorion / Q000378:metabolism; D002824:Chorionic Villi / Q000378:metabolism; D003656:Decidua / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism; D005091:Exons; D005321:Extraembryonic Membranes / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D016298:Hematopoietic Cell Growth Factors / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy / Q000378:metabolism*; D011261:Pregnancy Trimester, First; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019009:Proto-Oncogene Proteins c-kit; D011817:Rabbits; D016364:Reading Frames; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis*; D019089:Stem Cell Factor; D014327:Trophoblasts / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D016298:Hematopoietic Cell Growth Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases