Protective effects of E5, an antiendotoxin monoclonal antibody, in the ovine pulmonary circulation.
The cross-protective effects of a murine immunoglobulin M monoclonal antilipid A antibody (E5 MAb) were tested by challenging awake sheep with mixtures of in vitro incubated E5 MAb (0.02 mg/kg) with lipopolysaccharide (LPS, 0.02 micrograms/kg) derived from Escherichia coli O111:B4, E. coli O55:B5, or Serratia marcescens. Intravenous infusion of these LPS preparations without antibody into awake sheep produced a similar pattern of fever, leukopenia, plasma thromboxane B2 (TxB2) release, and acute pulmonary vasoconstriction with pulmonary hypertension. The addition of MAb E5 to LPS from E. coli O111:B4 reduced these responses to the LPS in a fashion comparable to that achieved with an MAb specific to the E. coli O111:B4 O-side chain. Incubation of LPS derived from E. coli O55:B5 with the E5 MAb only slightly diminished acute pulmonary hypertension, the delayed temperature increase, and the degree of leukopenia (all P = NS) but reduced the mean peak TxB2 at 60 min (P < 0.05) compared with a control infusion of E. coli O55:B5 LPS. We were unable to demonstrate any protective effects on the pulmonary circulation from incubating E5 with LPS derived from S. marcescens. Preincubation of B55 MAb (a murine immunoglobulin M MAb directed against a human milk fat globulin), the control antibody, with LPS from E. coli 0111:B4 decreased the mean peak TxB2 but had no effect on the other parameters. We conclude that incubating E5 with LPS protects the pulmonary circulation of sheep from challenge with LPS derived from the parent E. coli strain. There were trends toward protection by E5 against LPS from 055:B5 E. coli, but these did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
T Y
TY
Department of Anesthesia, Massachusetts General Hospital, Boston 02114.
Zapol
W M
WM
Greene
E
E
Robinson
D R
DR
Rubin
R H
RH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004926:Escherichia coli; D005260:Female; D006976:Hypertension, Pulmonary / Q000517:prevention & control; D007075:Immunoglobulin M / Q000276:immunology; D007958:Leukocyte Count / Q000187:drug effects; D007970:Leukopenia / Q000517:prevention & control; D008050:Lipid A / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology* / Q000633:toxicity; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects*; D012706:Serratia marcescens; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D008050:Lipid A; D008070:Lipopolysaccharides; D013929:Thromboxane B2