Matrix-associated transforming growth factor-beta 1 primes mouse bone marrow-derived mast cells for increased high-affinity Fc receptor for immunoglobulin E-dependent eicosanoid biosynthesis

Mast cells at different tissue locations are heterogeneous with respect to histochemical staining characteristics, granule protease and proteoglycan c ontent, and eicosanoid biosynthesis. We used Matrigel, an extract from the Engelbreth-Holm-Swarm mouse sarcoma that is enriched in basement-membrane p roteins, to investigate the effect of tissue matrix proteins on the differe ntiation of mouse mast cells, with particular attention to eicosanoid biosy nthesis, Culture of mouse bone-marrow cells in interleukin-3 on Matrigel fo r 3 to 4 wk provided a population of mast cells with more intense metachrom asia and increased safranin counterstaining compared with mast cells derive d in the absence of Matrigel (bone marrow-derived mast cells [BMMC]). High- affinity Fc receptor for immunoglobulin E-dependent biosynthesis of prostag landin D-2 and leukotriene (LT) C-4 was 6- and 11-fold higher, respectively , from mast cells derived in the presence of Matrigel compared with convent ional BMMC derived in its absence. BMMC derived in the presence of Matrigel also generated substantial quantities of 6-trans-LTB4 diastereoisomers and LTB4, which were minimally generated by conventional BMMC. When convention al BMMC derived in the absence of Matrigel were then cultured on Matrigel f or 5 d, eicosanoid biosynthesis was upregulated without any change in granu le staining characteristics. This upregulation in eicosanoid biosynthesis w as inhibited by neutralizing anti-transforming growth factor (TGF)-beta 1-s pecific antibodies, was reproduced by 1 ng/ml TGF-beta 1, and was attribute d to increased expression of cytosolic phospholipase A(2).