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Infection and Immunity, July 1999, p. 3284-3289, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Carrageenan Primes Leukocytes To Enhance Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Production

Masanori Ogata,1,* Takashi Matsui,2 Toshiro Kita,3 and Akio Shigematsu1

Department of Anesthesiology,1 Department of Molecular Biology,2 and Department of Forensic Medicine,3 School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

Received 7 December 1998/Returned for modification 24 February 1999/Accepted 2 April 1999

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.

* Corresponding author. Mailing address: Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu 807, Japan. Phone: (093) 691-7265. Fax: (093) 601-2910. E-mail: mogata{at}med.uoeh-u.ac.jp.

Infection and Immunity, July 1999, p. 3284-3289, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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