Published in Volume
102, Issue 11 (December 1, 1998)
J Clin Invest. 1998;102(11):2019–2027.
doi:10.1172/JCI4317.
Copyright ©
1998, The American Society for
Clinical Investigation.
Research Article
Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide.
K R Solomon, E A Kurt-Jones, R A Saladino, A M Stack, I F Dunn, M Ferretti, D Golenbock, G R Fleisher and R W Finberg
Infectious Disease Unit, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Published December 1, 1998
Septic shock induced by lipopolysaccharide (LPS) triggering of cytokine production from monocytes/macrophages is a major cause of morbidity and mortality. The major monocyte/macrophage LPS receptor is the glycosylphosphatidylinositol (GPI)-anchored glycoprotein CD14. Here we demonstrate that CD14 coimmunoprecipitates with Gi/Go heterotrimeric G proteins. Furthermore, we demonstrate that heterotrimeric G proteins specifically regulate CD14-mediated, LPS-induced mitogen-activated protein kinase (MAPK) activation and cytokine production in normal human monocytes and cultured cells. We report here that a G protein binding peptide protects rats from LPS-induced mortality, suggesting a functional linkage between a GPI-anchored receptor and the intracellular signaling molecules with which it is physically associated.
