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
Kk. Eklund et al., 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 Journal of experimental medicine, 180(1), 1994, pp. 67-73
The ear, skin, and purified serosal mast cells of WBB6F(1)/J-+/+ (WB-/+) and WCB6F(1)/J+/+ (WC-+/+) mice contain high steady-state levels o
f the transcripts that encode mouse mast cell protease (mMCP) 2, mMCP-
4, mMCP-5, mMCP-6, and mouse mast cell carboxypeptidase A (mMC-CPA). I
n 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 defect
s in their c-kit and c-kit ligand genes, respectively. We now report t
hat the immature bone marrow-derived mast cells (mBMMC) obtained in vi
tro 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 mM
CP-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 stead
y-state levels of five granule protease transcripts expressed by the m
ature serosal, ear, and skin mast cells of their normal +/+ littermate
s suggests that c-kit-mediated signal transduction is not essential fo
r inducing transcription of these protease genes. Because rIL-4 inhibi
ts 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-+/+ mBM
MC and W/W-v mBMMC was investigated. Although rIL-10 induced expressio
n of the mMCP-1 transcript in WC-+/+ and W/W-v mBMMC, rIL-4 was not ab
le to suppress the steady-state levels of the mMCP-1 transcript or any
other protease transcript in these cultured mast cells. Thus, not onl
y do BALB/cJ mBMMC express fewer granule proteases than mBMMC from mas
t cell-deficient strains and their normal littermates but the subseque
nt induction of late-expressed proteases in BALB/cJ mBMMC is more tigh
tly regulated by IL-3 and IL-4.