Direct cell-to-cell contact between Kupffer cells and hepatocytes augments endotoxin-induced hepatic injury

被引:58
作者
Hoebe, KHN
Witkamp, RF
Fink-Gremmels, J
Van Miert, ASJPAM
Monshouwer, M
机构
[1] Univ Utrecht, Fac Vet Med, Dept Vet Pharm Pharmacol & Toxicol, NL-3584 CM Utrecht, Netherlands
[2] TNO Pharma, Dept Pharmacol, NL-3704 HE Zeist, Netherlands
[3] Pharmacia & Upjohn Inc, Drug Metab Res, I-20014 Nerviano, Italy
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2001年 / 280卷 / 04期
关键词
lipopolysaccharide; cytokines; biotransformation; nitric oxide;
D O I
10.1152/ajpgi.2001.280.4.G720
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
This study focuses on the importance of direct contact between Kupffer cells (KCs) and hepatocytes (HCs) during the hepatic inflammatory response using an in vitro approach. The lipopolysaccharide (LPS)-induced inflammatory response in monocultures of porcine HCs and KCs were compared with cocultures prepared either with direct contact between KCs and HCs (DC cocultures) or without direct contact using cell culture membrane inserts. Our data show that DC cocultures exhibited the highest production of tumor necrosis factor (TNF)-alpha, interleukin-6, and nitric oxide (NO) compared with the other cultures. Immunohistochemical studies revealed that TNF-alpha was exclusively produced by KCs, whereas HCs were responsible for NO production after LPS stimulation. Biotransformation capacity, as determined by cytochrome P-450 and UDP glucuronosyl transferase enzyme activities, was most significantly decreased in DC cocultures. These results provide evidence that direct contact between KCs and HCs favors the extensive TNF-alpha production by KCs but in turn affects HC functionality and viability. These findings suggest that direct contact between KCs and HCs plays a key role in the development of a fulminating hepatic inflammatory response.
引用
收藏
页码:G720 / G728
页数:9
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