This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guyton, K. Articles by Cook, J. A. Search for Related Content PubMed Articles by Guyton, K. Articles by Cook, J. A. Social Bookmarking                   What's this?

Endotoxin-induced cross-tolerance to Gram-positive sepsis

Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA

Robert Bond

Department of Physiology, University of South Carolina School of Medicine, Columbia, South Carolina, USA

Cristina Romeo

Department of Microbiology, Medical University of Messina, Messina, Italy

Rodney Southern

Department of Physiology, Medical University of South Carolina, Charleston, South Carolina, USA

Joel Cochran

Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA

Giuseppe Teti

Department of Microbiology, Medical University of Messina, Messina, Italy

James A. Cook

Department of Physiology, Medical University of South Carolina, Charleston, South Carolina, USA

The manifestations of Gram-positive sepsis and Gram-negative sepsis share some common clinical features suggesting common pathways of activation. The goal of this study was to assess whether lipopolysaccharide (LPS) can produce cross-tolerance to Gram-positive sepsis induced by group B streptococcus (GBS). Thromboxane (TxB₂), tumor necrosis factor (TNF), and nitric oxide (NO) production by in vitro LPS- and heat killed GBS-stimulated rat peritoneal macrophages were measured. Since our previous studies have demonstrated altered macrophage activation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) in tolerance, we also examined the effect of LPS and killed GBS on ERK 1/2 activation in normal and LPS tolerant macrophages. Tolerance was induced in rats by intraperitoneal injection of Salmonella enteritidis LPS or vehicle for two consecutive days at doses of 0.1 and 0.5 mg/kg body weight. Three days after the second LPS dose, rats were injected intravenously with viable GBS (5 x l0⁹ cfu/kg) and D-galactosamine (1 g/kg). LPS tolerance significantly prolonged (P <0.05) mean survival time to severe GBS sepsis in D-galactosamine sensitized rats from 12.9 ± 1.7 h in control rats to 44.0 ± 8.9 h in tolerant rats. Peritoneal macrophages from LPS tolerant rats exhibited suppressed LPS induced in vitro TxB₂ and TNF production (P <0.05). Tolerance also decreased in vitro heat killed GBS-induced TNF production, but did not significantly affect TxB₂ production. NO production stimulated by LPS (10 µg/ml was not impaired in LPS tolerance; however at lower doses (0.02—1.25 µg/ml), NO production was significantly decreased (P <0.05). NO production was augmented (P <0.05) in response to stimulation with GBS (10 µg/ml) and unaltered at lower doses (0.02—1.25 µg/ml) in tolerant cells. LPS activated ERK 1/2 in control macrophages, but activation of ERK 1/2 was suppressed in LPS tolerance. GBS did not significantly affect ERK 1/2 activity in control or tolerant macrophages. Nevertheless, the selective mitogen-activated kinase (MAPK)/ERK kinase (MEK) inhibitor, PD 98059 blocked (P <0.05) both GBS- and LPS-induced TNF and TxB₂ production, but not NO production. Thus, some level of ERK 1/2 activity appears essential for GBS- and LPS-induced macrophage activation. In conclusion, LPS tolerance induces partial cross-tolerance to Gram-positive sepsis induced lethality, and alters LPS- and GBS-induced in vitro peritoneal macrophage mediator production. This suggests common pathways of cellular activation for GBS and LPS that are altered by LPS tolerance.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Guyton, R. Bond, C. Reilly, G. Gilkeson, P. Halushka, and J. Cook Differential effects of 15-deoxy-{Delta}12,14-prostaglandin J2 and a peroxisome proliferator-activated receptor {gamma} agonist on macrophage activation J. Leukoc. Biol., April 1, 2001; 69(4): 631 - 638. [Abstract] [Full Text]