Modulation of integrin expression during mast cell differentiation

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Abstract
Previously we have reported that rodent mast cells synthesize the mRNA encoding the α and β integrin chains (α4, β1 and β7) of the lymphocyte Peyer's patch adhesion molecule (LPAM)-1 and LPAM-2 lymphocyte homing receptors, and that they possess an α4-containing integrin complex on their cell surface. In this report, we have examined the expression of these integrin chain genes by mature connective tissue mast cells (CTMC) and by bone marrow-derived mast cells (BMMC) differentiated from bone marrow precursor cells in the presence of interleukin (IL)-3 and/or the c-kit ligand (also known as mast cell growth factor and stem cell growth factor). High levels of both the β7 and β1 transcripts were present in mature CTMC while those encoding the α4 chain were absent. Similarly, when BMMC were grown in IL-3 for 28 days and analyzed for integrin chain transcripts, those specific for the α4 chain were also diminished compared to β7 and β1 transcripts. To compare the expression of these integrin genes during mucosal mast cell and CTMC development, BMMC were derived in the presence of IL-3 alone, c-kit alone, or IL-3/c-kit together. These experiments indicated that c-kit inhibited the transcription of the β7 and FcεRI genes while enhancing α4 transcript levels. The enhancement of α4 levels, however, was abrogated with the addition of IL-3. Similarly, the c-kit-induced depression of β7 and Fcε RI transcript levels was overcome by the addition of IL-3. These data suggest that the integrin complexes synthesized by the mast cells may differ depending upon their path of differentiation and that another α chain integrin may be synthesized to complex with the β7 and/or β1 chains.