Mouse bone marrow-derived mast cells acquire responsiveness to substance P after co-culture with 3T3 fibroblasts in the presence of stem cell factor

Connective tissue-type mast cells degranulate in response to a neurogenic peptide, substance P, whereas bone marrow-derived mast cells (BMMC) do not respond to this stimulant when prepared with a combination of interleukin-3 and interleukin-4. In the present study we demonstrated that BMMC obtained from three different strains of mice, NC, BALB/c and C57BL/6, which are immature mast cells low in histamine content and unresponsive to substance F) increased 10 to 100-fold in their histamine content and acquired responsiveness to substance P after co-culture with NIH/3T3 fibroblasts in the presence of 10 ng/mL of stem cell factor (SCF). This change was observed after 1 week of co-culture and increased over a 3 week period, whereas 3T3 fibroblasts or SCF (100 ng/mL) alone was insufficient to duplicate this phenotypic change in BMMC. It is suggested that the response to substance P of mast cells is not through NK-1 receptors but rather through a different mechanism, since the reverse transcriptase-mediated polymerase chain reaction technique failed to show expression of NK-1 receptor mRNA in BMMC after co- culture as well as before co-culture.