title: Capture of lipopolysaccharide (endotoxin) by the blood clot: a comparative study.
abstract: In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot) and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument. Here we show that, in addition to these passive functions in immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus, and both the platelet thrombus and the fibrin clot of mammals (human, mouse) operate to capture lipopolysaccharide (LPS, endotoxin). The lipid A core of LPS is the principal agent of gram-negative septicemia, which is responsible for more than 100,000 human deaths annually in the United States and is similarly toxic to arthropods. Quantification using the Limulus Amebocyte Lysate (LAL) test shows that clots capture significant quantities of LPS and fluorescent-labeled LPS can be seen by microscopy to decorate the clot fibrils. Thrombi generated in the living mouse accumulate LPS in vivo. It is suggested that capture of LPS released from gram-negative bacteria entrapped by the blood clot operates to protect against the disease that might be caused by its systemic dispersal.
authors.affiliation: Marine Biological Laboratory, Woods Hole, Massachusetts, United States of America ; Department of Molecular and Cellular Biology, University of California Davis, Davis, California, United States of America.
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Armstrong
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Rickles
authors.forename: Peter B
authors.initials: PB
authors.lastname: Armstrong
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D005337:Fibrin / Q000378:metabolism / Q000502:physiology*; D006737:Horseshoe Crabs / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D008074:Lipoproteins / Q000097:blood / Q000502:physiology*; D051379:Mice; D013045:Species Specificity; D013925:Thromboplastin / Q000378:metabolism / Q000502:physiology*; D013927:Thrombosis / Q000382:microbiology
chemical_list: D008070:Lipopolysaccharides; D008074:Lipoproteins; D005337:Fibrin; D013925:Thromboplastin