An effector role for platelets in systemic and local lipopolysaccharide-induced toxicity in mice, mediated by a CD11a- and CD54-dependent interaction with endothelium.
The role of platelets was investigated in two models of lipopolysaccharide (LPS)-induced toxicity in mice: the systemic reaction, provoked by intravenous LPS injection in D-galactosamine-sensitized recipients, which results in host death, and the local reaction, elicited in the skin by sequential injections of LPS and tumor necrosis factor alpha at 24-h intervals, which results in hemorrhagic necrosis. In both models, the depletion of platelets with a rabbit polyclonal or a mouse monoclonal antiplatelet immunoglobulin G afforded significant protection. In the local reaction, studies of the distribution of 111In-labelled platelets as well as optical and electron microscopy showed that platelets are localized in the dermal venules before hemorrhage occurs. Anti-CD11a (LFA-1) and anti-CD54 (ICAM-1) monoclonal antibodies prevented both platelet localization and hemorrhagic necrosis, and these determinants were detected on mouse platelets by immunofluorescence. The antiplatelet monoclonal antibody did not reduce the localization of polymorphonuclear leukocytes in the dermal venules, as shown by histological sections. Thus, in the local reaction, the stimulation with LPS and tumor necrosis factor alpha leads to a binding of platelets to the endothelium of venules by their beta 2 integrins, which seems necessary for the development of the hemorrhagic necrosis.
Piguet
P F
PF
Department of Pathology, University of Geneva, Switzerland.
Vesin
C
C
Ryser
J E
JE
Senaldi
G
G
Grau
G E
GE
Tacchini-Cottier
F
F
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005688:Galactosamine / Q000008:administration & dosage; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides / Q000633:toxicity*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005688:Galactosamine