Protective effects of anti-O polysaccharide and anti-lipid A monoclonal antibodies on pulmonary hemodynamics.
Monoclonal antibodies (MAbs) directed to endotoxin can protect in some animal models against the pathophysiological effects of endotoxin infusion. When 0.02 microgram/kg of lipopolysaccharide (LPS) derived from Escherichia coli O111:B4 was incubated in vitro for 2 h with the murine immunoglobulin G MAb, 5B10, directed against the O-polysaccharide antigenic domain of E. coli O111:B4 and then the mixture was infused into sheep, we noted significant protection. The second temperature peak was decreased (P < 0.05 vs. LPS control). The acute pulmonary arterial pressure elevation was diminished (mean peak pulmonary arterial pressure 23.2 +/- 2.5 mmHg, P < 0.05 vs. LPS control), and the peak plasma thromboxane B2 level was reduced (mean peak thromboxane B2 level 0.50 +/- 0.15 ng/ml, P < 0.05 vs. LPS control). In contrast, preincubation of the LPS with a human immunoglobulin M MAb, HA-1A, directed against the core glycolipid of the LPS molecule provided no protective effects in this sheep model. This finding is in agreement with recent studies reporting HA-1A may bind to antibiotic-treated bacteria but not to purified smooth LPS.
Chen
T Y
TY
Department of Anesthesia, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Warren
H S
HS
Greene
E
E
Black
K M
KM
Frostell
C G
CG
Robinson
D R
DR
Zapol
W M
WM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004926:Escherichia coli / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007958:Leukocyte Count / Q000187:drug effects; D008050:Lipid A / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D011651:Pulmonary Artery / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D008050:Lipid A; D008070:Lipopolysaccharides; D013929:Thromboxane B2