Antilipid A monoclonal antibody HA-1A decreases the capacity of bacterial lipopolysaccharide to activate human vascular endothelial cells by an immune adherence mechanism.
Human monoclonal IgM antibody HA-1A, which recognizes the lipid A component of bacterial lipopolysaccharide (LPS), has been shown to reduce mortality in Gram negative septicemia. The vascular endothelial lining of blood vessels, which controls leucocyte traffic and activation, as well as haemostatic balance, may be one of the primary targets of LPS action during sepsis. In earlier studies we have described HA-1A-induced immune adherence of LPS to complement receptors on erythrocytes, and showed that pre-incubation with HA-1A, in the presence of complement and red blood cells, markedly reduced LPS-induced cytokine production from peripheral blood mononuclear cells. In the present study, we measured the effect of immune adherence of LPS in the presence of HA-1A on the responses of cultured endothelial cells, and found that subsequent expression of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and secretion of the cytokines interleukin-6 and granulocyte-macrophage colony stimulating factor were markedly reduced. Moreover, the ability of LPS to increase levels of tissue factor procoagulant activity on endothelial cells was markedly diminished by LPS immune adherence to HA-1A. This decrease in endothelial activation in response to LPS following immune adherence to HA-1A may play a significant role in the protective effect of HA-1A in vivo during the course of Gram negative sepsis.
Paleolog
E M
EM
Kennedy Institute of Rheumatology, Sunley Division, London, UK.
Katsikis
P
P
Harris
G
G
Daddona
P
P
Dalesandro
M R
MR
Kinney
C S
CS
Woody
J N
JN
Feldmann
M
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008050:Lipid A / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008050:Lipid A; D008070:Lipopolysaccharides; D013925:Thromboplastin