Respective role of polymorphonuclear leukocytes and their integrins (CD-11/18) in the local or systemic toxicity of lipopolysaccharide.
The role of neutrophils (PMNs) and leukocyte integrins was investigated in two models of lipopolysaccharide (LPS)-induced toxicity: the systemic lethality assay in D-galactosamine-sensitized mice and the local reaction elicited by intradermal injection of LPS and tumor necrosis factor (TNF) at 24-h intervals. In the local reaction, depletion of PMNs with an anti-PMN monoclonal antibody (mAb) and mAbs against CD-11a (or LFA1) and CD-11b (or CR3) completely prevented the hemorrhagic necrosis. Evaluation of histological sections and myeloperoxidase levels suggested different mechanism of protection because PMNs were abundant in anti-CD-11- and absent in anti-PMN-treated mice. In the systemic assay, depletion of PMNs ensured 100% survival, whereas after administration of anti-CD-11a or b mAb, the percentages of survivors were 6 and 59%, respectively. One hour after LPS injection, the serum TNF-alpha level was higher in PMN-depleted mice than in controls. These studies provide evidence that neutrophils are essential for the expression of local or systemic LPS-induced injury, whereas the requirement for their leukocytic integrins is obvious only in the local reaction.
Chang
H R
HR
Department of Genetics and Microbiology, University of Geneva, Switzerland.
Vesin
C
C
Grau
G E
GE
Pointaire
P
P
Arsenijevic
D
D
Strath
M
M
Pechère
J C
JC
Piguet
P F
PF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha