Regulation and possible function of axl expression in immature human mast cells.
The receptor tyrosine kinase Axl which expresses extracellular domains reminiscent of cell adhesion molecules, is involved in homotypic binding as well as in intracellular signaling of myeloid progenitor cells. In order to investigate factors which might influence differentiation pathways through changes of the adhesive properties of cells, we analyzed the expression of axl in immature basophil and mast cell lines and in cultured basophil and mast cell precursors. Axl expression was induced by interferon-alpha in the human leukemic mast cell line HMC-1 and in cultured mast cells derived from CD34+ peripheral blood cells. Axl induction was dose dependent, appeared within 1 h, and was independent of de novo protein synthesis. IFNalpha-treated HMC-1 cells expressing axl formed large cell aggregates within 40 h while untreated cells did not. HMC-1 cells also expressed gas6, the putative ligand of axl, which has been shown to induce axl-mediated homotypic binding. Gas6 expression was independent of interferon treatment in HMC-1 cells. The present results suggest that axl-mediated changes of cellular adhesive properties in mast cells may be important in mast cell differentiation as well as in mast cell-associated inflammation.
Heide
I
I
Experimental Dermatology, Charité-Virchow Klinikum Humboldt-Universität Berlin, Germany.
Sokoll
A C
AC
Henz
B M
BM
Nagel
S
S
Kreissig
K
K
Grützkau
A
A
Grabbe
J
J
Wittig
B
B
Neubauer
A
A
D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism; D013736:Testicular Neoplasms / Q000097:blood; D013997:Time Factors; D000094963:Axl Receptor Tyrosine Kinase
D016898:Interferon-alpha; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D003513:Cycloheximide; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human