Induction of angiotensin converting enzyme in cultured human monocytes by a factor present in the bronchoalveolar lavage fluid of sarcoidosis patients.
Human peripheral blood monocytes synthesize a low level of angiotensin converting enzyme (ACE) when cultured in vitro for six days. If cell-free bronchoalveolar lavage fluid from sarcoidosis patients was included with the monocytes during culture, the monocyte ACE level increased significantly in a dose dependent manner. In contrast, the cell-free bronchoalveolar lavage fluid from control subjects and patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis raised basal monocyte levels little, if at all. These results suggested that sarcoid lavage fluid contains a soluble ACE-inducing factor (AIF) that was absent or present in much lower concentrations in the bronchoalveolar lavage fluid of the other patients studied. Initial attempts to characterize this AIF indicated an apparent molecular weight of greater than 5000 daltons as determined by Amicon ultrafiltration. The AIF was stable to heating at 56 degrees for 1 hour. This finding demonstrated that lavage ACE was not responsible for the AIF activity since lavage ACE is inactivated under these conditions. Gamma-interferon (macrophage-activating factor) was also eliminated as the agent responsible for AIF activity since gamma-interferon decreased rather than increased monocyte ACE. In summary, bronchoalveolar lavage fluid from sarcoid patients contains a soluble factor (AIF) that induces ACE in cultured monocytes. Action of this factor in vivo may be responsible for the increased ACE levels seen in the monocyte-derived epithelioid granuloma cells of sarcoidosis.
Rohrbach
M S
MS
Thoracic Diseases Research Unit, Mayo Clinic, Rochester, MN 55905.
Vuk-Pavlović
Z
Z
Martin
W J
WJ
DeLaval
P
P
Genetet
N
N
D000328:Adult; D000542:Alveolitis, Extrinsic Allergic / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis*; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000378:metabolism; D012507:Sarcoidosis / Q000378:metabolism*
D007371:Interferon-gamma; D007703:Peptidyl-Dipeptidase A