Altered metabolism of mast-cell growth factor (c-kit ligand) in cutaneous mastocytosis.
METHODS
The lesions of cutaneous mastocytosis are characterized by dermal infiltrates of mast cells and may appear hyperpigmented because of the presence of increased levels of epidermal melanin. Mast-cell growth factor, the ligand for the product of the c-kit proto-oncogene, stimulates the proliferation of mast cells and increases the production of melanin by melanocytes. We therefore looked for the expression of the mast-cell growth factor gene in the skin of patients with cutaneous mastocytosis using immunohistochemical techniques and the polymerase chain reaction.


RESULTS
In the skin of normal subjects and those with unrelated diseases, immunoreactive mast-cell growth factor was associated with keratinocytes and scattered dermal cells, a pattern consistent with cell-bound mast-cell growth factor. In skin samples containing lesions and in clinically normal skin from patients with mastocytosis, however, mast-cell growth factor was also found free in the dermis and in the extracellular spaces between keratinocytes, suggesting the presence of a soluble form of this protein. Messenger RNA (mRNA) that can encode soluble mast-cell growth factor was present in the skin of patients as well as in that of normal control subjects. No sequence abnormalities were detected in mRNA for mast-cell growth factor from one patient.


CONCLUSIONS
The altered distribution of mast-cell growth factor in the skin of patients with cutaneous mastocytosis is consistent with abnormal production of the soluble form of this factor. This abnormality is probably due to increased proteolytic processing, since it was not explained by differences in the splicing or sequence of mast-cell growth factor mRNA in the patients. Soluble mast-cell growth factor may cause the characteristic accumulation of mast cells and the hyperpigmentation of skin found in cutaneous mastocytosis. These findings suggest that some forms of mastocytosis represent reactive hyperplasia rather than mast-cell neoplasia.
Longley
B J
BJ
Department of Dermatology, Yale University School of Medicine, New Haven, Conn 06510.
Morganroth
G S
GS
Tyrrell
L
L
Ding
T G
TG
Anderson
D M
DM
Williams
D E
DE
Halaban
R
R
D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000378:metabolism; D008024:Ligands; D008297:Male; D008415:Mastocytosis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D019089:Stem Cell Factor
D016298:Hematopoietic Cell Growth Factors; D008024:Ligands; C000715470:MAS1 protein, human; D015345:Oligonucleotide Probes; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D019089:Stem Cell Factor