CYTOKINE MODULATABLE SIGNALING THROUGH MACROPHAGE HLA CLASS-II .1. IFN-GAMMA UP-REGULATES THE EFFICIENCY OF CA2-DP( MOBILIZATION IN RESPONSE TO LIGATION OF MACROPHAGE HLA)
Dp. Dialynas et al., CYTOKINE MODULATABLE SIGNALING THROUGH MACROPHAGE HLA CLASS-II .1. IFN-GAMMA UP-REGULATES THE EFFICIENCY OF CA2-DP( MOBILIZATION IN RESPONSE TO LIGATION OF MACROPHAGE HLA), Journal of interferon & cytokine research, 17(11), 1997, pp. 671-679
The human macrophage line 2MAC, established recently from peripheral b
lood, expresses a number of lineage-specific markers as well as a broa
d array of intercellular adhesion molecules, including high levels of
HLA class I and class II. We have presented evidence elsewhere that 2M
AC can be productively applied to the study of signal transduction thr
ough macrophage HLA class II. Namely, we showed that ligation of 2MAC
HLA class II, but not HLA class I, by monoclonal antibody (mAb) elicit
s an increase in free cytoplasmic Ca2+ concentration [Ca2+](i). Moreov
er, this Ca2+ flux appears to be functionally relevant: ligation of HL
A-DR, but not HLA class I, by mAb results in the Ca2+ mobilization-dep
endent induction of tissue factor, the high-affinity cellular receptor
for factor VII/VIIa. Here we show that 2MAC is uniquely valuable for
addressing the efficiency of signal transduction through HLA class II.
Namely, we show here that prior culture of 2MAC cells with interferon
-gamma (IFN-gamma) profoundly upregulates subsequent Ca2+ mobilization
in response to ligation of HLA-DP in the absence of increased cell su
rface HLA-DP expression. Because IFN-gamma has no effect on 2MAC HLA-D
P expression, IFN-gamma must upregulate Ca2+ mobilization by increasin
g the efficiency of signal transduction through HLA class II (HLA-DP),
by targeting some other component of the macrophage HLA class II sign
alling pathway.