Poor response of cultured mast cells derived from mi/mi mutant mice to nerve growth factor.
Decreased numbers of mast cells and abnormalities in the phenotype of mast cells are observed in the skin of mi/mi mutant mice. Recently, the mi locus was identified to encode a novel member of the basic-helix-loop-helix-leucine zipper protein family of transcription factors. Since nerve growth factor (NGF) has been reported to influence the proliferation and the phenotype of cultured mast cells (CMCs), we compared the effect of NGF between mi/mi and control normal (+/+) CMCs. Addition of NGF to the suboptimal dose of recombinant murine interleukin-3 (rmIL-3) increased the plating efficiency of +/+ CMCs, but not of mi/mi CMCs. Although +/+ CMCs were berberine sulfate-negative when cultured with rmIL-3 alone, +/+ CMCs became berberine sulfate-positive when cultured in the presence of both rmIL-3 and NGF, which suggests increased heparin content. In contrast, NGF did not influence the phenotype of mi/mi CMCs. +/+ CMCs significantly bound 125I-NGF, but mi/mi CMCs did not, which suggests a defect of NGF receptors in mi/mi CMCs. Both p75 and p140 molecules are known to be involved in the formation of NGF receptors. Although the expression of p140 messenger (m)RNA was comparable between +/+ and mi/mi CMCs, the expression of p75 mRNA was significantly lower in mi/mi CMCs than in +/+ CMCs. Taken together, the poor response of mi/mi CMCs to NGF appeared to be attributable to the impaired transcription of the p75 gene.
Jippo
T
T
Department of Pathology, Osaka University Medical School, Japan.
Ushio
H
H
Hirota
S
S
Mizuno
H
H
Yamatodani
A
A
Nomura
S
S
Matsuda
H
H
Kitamura
Y
Y
D000818:Animals; D001483:Base Sequence; D002268:Carboxypeptidases / Q000235:genetics; D043422:Carboxypeptidases A; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006636:Histamine Release / Q000187:drug effects; D017403:In Situ Hybridization; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008817:Mice, Mutant Strains; D051739:Microphthalmia-Associated Transcription Factor; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology; D053802:Tryptases
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; C509190:Tpsb2 protein, mouse; D014157:Transcription Factors; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D012697:Serine Endopeptidases; C066932:mast cell protease 4; C509222:Tpsab1 protein, mouse; D053802:Tryptases