Mouse gp49B is an immunoreceptor tyrosine-based inhibitory motif-bearing re
ceptor identified on mast cells and NK cells. In this report, however, we s
how that this receptor is expressed on macrophages accumulating in the uter
ine metrial gland in midgestation, along with gp49A that has a very homolog
ous extracellular domain with gp49B but has a short cytoplasmic domain with
out ITIM. Culture of bone marrow cells in the conditioned medium of the met
rial gland resulted in the selective proliferation of macrophages expressin
g both Fc gamma -activating receptors and gp49B inhibitory receptor. Stimul
ation of macrophages with immobilized IgG, but not with anti-Fc gamma RII/I
II, induced a considerable amount of TNF-alpha and IL-10 production, sugges
ting that the high-affinity receptor for IgG (Fc gamma RI) can transmit act
ivating signals in cytokine production of macrophages. Furthermore, coligat
ion of gp49B with Fc gamma RI resulted in the inhibition of TNF-alpha produ
ction. Thus, our data provide evidence that gp49B is an endogenous negative
regulator of macrophage activation and may regulate the function of macrop
hages during pregnancy.