Angiotensin II binding to human mononuclear cells.
Serum angiotensin converting enzyme activity is elevated in certain human granulomatous diseases. Angiotensin II modestly suppresses thymidine incorporation and augments gamma interferon production from human blood mononuclear cells. This suggests that angiotensin II may play an immunoregulatory role in human granulomatous inflammation. For this reason, the binding of angiotensin II to human peripheral blood mixed mononuclear cells, and to the human monocyte-like cell line, U-937, was studied. Angiotensin II binding to U-937 cells reveals a low level of saturable specific binding (Kd = 3 x 10(-10) M). However, binding to human cells is not easily reversible and is poorly inhibited in a competitive manner. In addition, the molecular integrity of the radioligand is not maintained following binding. Therefore, the definition of classical receptor binding cannot be fulfilled. Since binding is decreased by low temperatures and various metabolic inhibitors, it appears likely that endocytosis occurs, perhaps along with receptor binding. Angiotensin II or its breakdown products modulate the production of monocyte cAMP in spite of the inability to demonstrate classical cell surface receptors.
Simon
M R
MR
Medical Service, Veterans Administration Medical Center, Allen Park, MI 48101.
Kamlay
M T
MT
Khan
M
M
Melmon
K
K
D000804:Angiotensin II / Q000097:blood* / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D000242:Cyclic AMP / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism
D000804:Angiotensin II; D000242:Cyclic AMP