Mm. Monick et al., Human alveolar macrophages are markedly deficient in REF-1 and AP-1 DNA binding activity, J BIOL CHEM, 274(25), 1999, pp. 18075-18080
Although many functions of human alveolar macrophages are altered compared
with their precursor cell, the blood monocyte (monocyte), the reason(s) for
these functional changes have not been determined. We recently reported th
at human alveolar macrophages do not express AP-1 DNA binding activity (Mon
ick, M. RI., Carter, A B., Gudmundsson, G;., Geist, L, J,, and Hunninghake,
G;. W, (1998) Am, J, Physiol, 275, L389-L397). To determine why alveolar m
acrophages do not express AP-1 DNA binding activity, we first showed that t
here was not a decrease in expression of the FOS and JUN proteins that make
up the AP-1 complex. There was, however, a significant difference in the a
mounts of the nuclear protein, REF-1 (which regulates AP-1 DNA: binding by
altering the redox status of FOS and JUN proteins), in alveolar macrophages
compared with monocytes, In addition, in vitro differentiation of monocyte
s to a macrophage-like cell resulted in decreased amounts of REF-1, Finally
, addition of REF-1 from activated monocytes to alveolar macrophage nuclear
proteins resulted in a marked increase in AP-1 DNA binding, These studies
strongly suggest that the process of differentiation of monocytes into alve
olar macrophages is associated with a loss of REF-1 and AP-1 activity. This
observation may explain, in part, some of the functional differences obser
ved for alveolar macrophages compared with monocytes.