Tetraacylated lipopolysaccharide of Yersinia pestis can inhibit multiple Toll-like receptor-mediated signaling pathways in human dendritic cells.

Background: Yersinia pestis, the causative agent of plague, showed a temperature-dependent change in lipid A composition, with a reduced degree of acylation when bacteria were grown at 37 degrees C (tetraacylated) versus ambient temperature (hexaacylated).

Methods: Human monocytes and monocyte-derived dendritic cells (DCs) were exposed to Y. pestis grown at 26 degrees C or 37 degrees C, to their corresponding lipopolysaccharides (LPS-26 degrees C or LPS-37 degrees C), and to ligands of different Toll-like receptors (TLRs), such as LPS from Escherichia coli (TLR4), lipoprotein (TLR2), polyinosinic-polycytidylic acid (poly-IC) (TLR9), and their combinations.

Levofloxacin rescues mice from lethal intra-nasal infections with virulent Francisella tularensis and induces immunity and production of protective antibody.

The ability to protect mice against respiratory infections with virulent Francisella tularensis has been problematic and the role of antibody-versus-cell-mediated immunity controversial. In this study, we tested the hypothesis that protective immunity can develop in mice that were given antibiotic therapy following infection via the respiratory tract with F. tularensis SCHU S4.

Critical role for serum opsonins and complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in phagocytosis of Francisella tularensis by human dendritic cells (DC): uptake of Francisella leads to activation of immature DC and intracellular survival of the bacteria.

Francisella tularensis is one of the most infectious human pathogens known. Although much has been learned about the immune response of mice using an attenuated live vaccine strain (LVS) derived from F. tularensis subspecies holarctica (Type B), little is known about the responses of human monocyte-derived immature dendritic cells (DC).

Cholera toxin and Salmonella typhimurium induce different cytokine profiles in the gastrointestinal tract.

Salmonella infection of the gastrointestinal tract (GT) results in fluid secretion and inflammation. In contrast, cholera toxin (CT) induces fluid secretion but no inflammation. Using a murine ligated intestinal loop model, we investigated cytokine production (interleukin-1 [IL-1], IL-2, IL-4, IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha) in the GT following exposure to these agents.

Effect of prostaglandin E on immune function in normal healthy volunteers.

Prostaglandin E (PGE) has been hypothesized to be the endogenous metabolite that results in the immunosuppression seen in patients with tumor and trauma. This has resulted in multiple investigators proposing that administration of PGE inhibitors, such as aspirin and indomethacin, might improve immune function in such patients. We administered a long acting PGE analog, misoprostol, to nine normal healthy volunteers for five days and assayed immune function before and after therapy.

Heart cyclic nucleotide responses to sustained aortic constriction in neonatal and adult rats.

The present studies examined adenosine and guanosine 3',5'-cyclic monophosphate (cAMP and cGMP) levels in left ventricular tissue of neonatal and adult rats subjected to 3-10 days of abdominal aortic constriction. Left ventricular cAMP levels were elevated after 3 days of pressure overloading in neonatal rats (2,274 +/- 430 pmol/g; mean +/- SE) compared with composite control values (1,280 +/- 124) obtained from sham-operated neonates, sham-operated adults, and aortic-constricted adult groups. cAMP levels declined progressively until, at 10 days after aortic constriction, values were lower (681 +/- 25 pmol/g) than control (1,621 +/- 107).

Metabolic enzyme response in the pressure-overloaded heart of weanling and adult rats.

Weanling and adult rats were subjected to left ventricular pressure overload induced by abdominal aortic constriction. At 5 days or 5 weeks postsurgery, the left ventricle (LV) was dissected, weighed, and metabolic marker enzyme activities (mumole/g/min) of tissue homogenates were measured. Enzymes representing glycolytic (phosphofructokinase (PFK] and mitochondrial (citrate synthase (CS) and malate dehydrogenase (MDH] metabolisms were evaluated.

Hemodynamic responses to methoxamine in exercise-conditioned and aorta-constricted rats.

Hemodynamic responses to methoxamine hydrochloride (Vasoxyl) were determined in rats conditioned by a moderate treadmill exercise program and in rats subjected to 5 wk of abdominal aortic constriction. Rats of comparable age served as controls. Initial hemodynamic values for control rats were as follows: left ventricular pressure, 124 +/- 4 Torr and cardiac index, 145 +/- 8 ml .