MOUSE BONE-MARROW-DERIVED MAST-CELLS (MBMMC) OBTAINED IN-VITRO FROM MICE THAT ARE MAST CELL-DEFICIENT IN-VIVO EXPRESS THE SAME PANEL OF GRANULE PROTEASES AS MBMMC AND SEROSAL MAST-CELLS FROM THEIR NORMAL LITTERMATES

The ear, skin, and purified serosal mast cells of WBB6F(1)/J-+/+ (WB-+/+) and WCB6F(1)/J+/+ (WC-+/+) mice contain high steady-state levels of the transcripts that encode mouse mast cell protease (mMCP) 2, mMCP-4, mMCP-5, mMCP-6, and mouse mast cell carboxypeptidase A (mMC-CPA). In contrast, no mast cell protease transcripts are present in abundance in the ear and skin of WBB6F(1)/J-W/W-v (W/W-v) and WCB6F(1)/J-Sl/Sl(d) (Sl/Sl(d)) mice which are mast cell-deficient in vivo due to defects in their c-kit and c-kit ligand genes, respectively. We now report that the immature bone marrow-derived mast cells (mBMMC) obtained in vitro with recombinant interleukin 3 (rIL-3) or WEHI-3 cell conditioned medium from WB-+/+, WC-+/+, W/W-v, and Sl/Sl(d) mice all contain high steady-state levels of the mMCP-2, mMCP-4, mMCP-5, mMCP-6, and mMC-CPA transcripts. As assessed immunohistochemically, mMCP-2 protein and mMCP-5 protein are also present in the granules of mBMMC from WB-+/+, WC-+/+, and W/W-v mice. That Sl/Sl(d) and W/W-v mBMMC contain high steady-state levels of five granule protease transcripts expressed by the mature serosal, ear, and skin mast cells of their normal +/+ littermates suggests that c-kit-mediated signal transduction is not essential for inducing transcription of these protease genes. Because rIL-4 inhibits the rIL-10-induced expression of mMCP-1 and mMCP-2 in BALB/cJ mBMMC, the ability of rIL-4 to influence protease mRNA levels in WC-+/+ mBMMC and W/W-v mBMMC was investigated. Although rIL-10 induced expression of the mMCP-1 transcript in WC-+/+ and W/W-v mBMMC, rIL-4 was not able to suppress the steady-state levels of the mMCP-1 transcript or any other protease transcript in these cultured mast cells. Thus, not only do BALB/cJ mBMMC express fewer granule proteases than mBMMC from mast cell-deficient strains and their normal littermates but the subsequent induction of late-expressed proteases in BALB/cJ mBMMC is more tightly regulated by IL-3 and IL-4.