Anti-lipid A monoclonal antibodies alter human endothelial cell ICAM-1 expression in vitro.
Two murine anti-lipid A MAbs (A78S1 and A523), which were protective in a rat model of neonatal endotoxin shock (Goto, M, Zeller WP, Hurley RM, Jong JS, Lee C-H: Prophylaxis and treatment of newborn endotoxic shock with anti-lipid A monoclonal antibodies. Circ Shock 35:60-64, 1991), were tested for their effects on lipid A-induced ICAM-1 expression by cultured human umbilical vein endothelial cells (HUVEC). In the presence of 5% fetal bovine serum, lipid A-induced ICAM-1 expression, as measured by radioimmunoassay following 18 h incubation, was enhanced by A78S1 at lower concentrations (.02-.2 micrograms/ mL) but was inhibited at concentrations of 20 micrograms/mL or greater. Its control immunoglobulin, purified nonspecific IgG2b, enhanced the lipid A-stimulated ICAM expression at all concentrations tested. Neither MAb A523 nor its control immunoglobulin, purified nonspecific IgM, had effects on the lipid A-stimulated ICAM-1 by HUVEC. Although A78S1 and A523 had no direct effects, the control immunoglobulins marginally stimulated ICAM-1 activity at their highest concentrations (possibly due to the presence of endotoxin). Furthermore, in serum-free medium all of the immunoglobulins dose-dependently stimulated ICAM-1 expression. These results demonstrate that anti-lipid A MAbs and other immunoglobulins can exhibit variable effects on unstimulated or lipid A-stimulated ICAM-1 expression by HUVEC depending upon the presence of serum, their concentration, immunoglobulin subclass, or epitope specificity.
Renzi
P M
PM
Septic Shock Research Program, Naval Medical Research Institute, National Naval Medical Center, Bethesda, Maryland 20889, USA.
Lee
C H
CH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000937:Antigen-Antibody Reactions / Q000187:drug effects; D002448:Cell Adhesion; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007962:Leukocytes; D008050:Lipid A / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D011112:Polymyxin B / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D016895:Culture Media, Serum-Free; D008050:Lipid A; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1; D011112:Polymyxin B