Carrageenan primes leukocytes to enhance lipopolysaccharide-induced tumor necrosis factor alpha production.
We have previously reported that pretreatment with carrageenan (CAR) enhances lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production in and lethality for mice. Whole blood cultured in vitro was used to show that CAR pretreatment results in about a 200-fold increase in LPS-induced TNF-alpha production. CAR by itself did not induce TNF-alpha production. However, CAR-treated cultured medium sensitized whole blood to make more LPS-induced TNF than did saline-treated cultured medium in vitro. It was also demonstrated that CAR pretreatment increases TNF-alpha mRNA levels of both blood cells and peritoneal exudate cells, but not of bone marrow cells. Immunoelectron microscopic analysis revealed that polymorphonuclear leukocytes and macrophages are TNF-alpha-producing cells in CAR-treated mice. In CAR-treated mice, TNF-alpha was seen early after LPS injection in leukocytes in hepatic sinusoids and on the surfaces of endothelial cells. TNF-alpha was also detected late after LPS injection in hepatocytes which become edematous. These results suggest that CAR primes leukocytes to produce TNF-alpha in response to LPS and that they play an important role in the pathogenesis of liver injury.
Ogata
M
M
Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. mogata@med.uoeh-u.ac.jp
Matsui
T
T
Kita
T
T
Shigematsu
A
A
D000818:Animals; D002351:Carrageenan / Q000494:pharmacology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004357:Drug Synergism; D005079:Excipients / Q000494:pharmacology*; D007962:Leukocytes / Q000378:metabolism* / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008854:Microscopy, Electron; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D017077:Culture Media, Conditioned; D005079:Excipients; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002351:Carrageenan