Type VIII collagen is a short-chain
collagen that is present in increased amounts in atherosclerotic lesions. Although the physiological function of this matrix
protein is unclear, recent data suggest an important role in tissue remodeling.
Type VIII collagen in the atherosclerotic lesion is mainly derived from smooth muscle cells. We now show that macrophages in the atherosclerotic vessel wall and monocytes in adjacent mural thrombi also express
type VIII collagen. We demonstrated this using a novel combined fluorescence technique that simultaneously stains, within the same tissue section, specific RNAs by in situ hybridization and
proteins by indirect immunofluorescence. In culture, human monocyte/macrophages expressed
type VIII collagen at all time points from 1 h to 3 wk after isolation. Western blotting and immunoprecipitation also revealed secretion of
type VIII collagen into the medium of 14-day-old macrophages. Because this is the first report of secretion of a
collagen by macrophages, we tested the effect of
lipopolysaccharide (LPS) and
interferon gamma, substances that stimulate macrophages to secrete lytic
enzymes, on macrophage expression of
type VIII collagen. LPS and
interferon gamma decreased expression of
type VIII collagen. By contrast, secretion of
matrix metalloproteinase 1 (
MMP 1) was increased, indicating a switch from a
collagen-producing to a degradative phenotype. Double in situ hybridization studies of expression of
type VIII collagen and
MMP 1 in human coronary arteries showed that in regions important for plaque stability, the ratio of
MMP 1
RNA to macrophage
type VIII collagen RNA varies widely, indicating that the transition from one phenotype to the other that we observed in vitro may also occur in vivo.