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Department of Biochemistry and Biophysics, Iowa State University, Ames, IA 50011
Granulated metrial gland (GMG) cells are NK cells that proliferate
and differentiate within the murine uterus during pregnancy. They have
been predicted to play important roles in nurturing the embryo, normal
placentation, and uterine tissue remodeling. GMG cell differentiation
is manifested by the accumulation of the cytolytic mediators, perforin,
granzyme A, and granzyme B, within cytoplasmic granules. The signaling
mechanisms required for GMG cell differentiation are largely unknown,
although recent in vitro assays have implicated IL-15 in these events.
In this report, we demonstrate that granzymes D, E, F, and G (granzymes
D–G) are also expressed in GMG cells but at a later stage in pregnancy
when compared with granzyme A expression. Whereas granzyme A is
expressed in early to mid-gestation, the expression of granzymes D–G
peak in mid- to late gestation. In addition, we show that the
expression patterns of IL-2Rß and the IL-2R
mRNAs overlap with
that of granzyme D–G mRNAs in the pregnant uterus. Finally, we
demonstrate that granzymes D–G are up-regulated by IL-2 and IL-15 in
primary cultures containing GMG cells. Taken together, these results
suggest that IL-2 and/or IL-15 may regulate GMG cell differentiation in
vivo, and that granzymes D–G may have different functions than
granzyme A during pregnancy.
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