CGP-42112 PARTIALLY ACTIVATES HUMAN MONOCYTES AND REDUCES THEIR STIMULATION BY LIPOPOLYSACCHARIDES

Citation
G. Egidy et al., CGP-42112 PARTIALLY ACTIVATES HUMAN MONOCYTES AND REDUCES THEIR STIMULATION BY LIPOPOLYSACCHARIDES, American journal of physiology. Cell physiology, 42(3), 1997, pp. 826-833
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
ISSN journal
0363-6143
Volume
42
Issue
3
Year of publication
1997
Pages
826 - 833
Database
ISI
SICI code
0363-6143(1997)42:3<826:CPAHMA>2.0.ZU;2-8
Abstract
CGP 42112, a high-affinity Ligand for angiotensin II AT(2) receptors, binds to rat macrophage/microglia lacking AT(2) receptors. Here we rep ort that CGP-42112 binds to human monocytes and exerts specific effect s. Binding studies revealed a single site, highly specific for CGP-421 12, not displaceable by angiotensin II, angiotensin fragments, tumor n ecrosis factor-alpha (TNF-alpha), interleukin (IL)-4, IL-IO, transform ing growth factor-beta, or lipopolysaccharide (LPS). Incubation of pur ified human monocytes in serum-free medium with CGP-42112 enhanced, in a dose-dependent manner, cell attachment to fibronectin and collagen- coated dishes as well as matrix metalloproteinase-9 secretion. CGP-421 12 did not promote cytokine secretion. In contrast, when added in the presence of low doses of LPS, CGP-42112 reduced the LPS-stimulated sec retion of TNF-alpha, IL-1 alpha, IL-1 beta, and. IL-6 without affectin g IL-10 and decreased the LPS-stimulated matrix metalloproteinase-9 ac tivity. Additionally, CGP-42112 inhibited the increase in protein kina se A activity produced by LPS. Our results indicate that CGP-42112 may modulate monocyte activation through binding to a novel receptor.