Interspecies variations in Bordetella catecholamine receptor gene regulation and function.

Bordetella bronchiseptica can use catecholamines to obtain iron from transferrin and lactoferrin via uptake pathways involving the BfrA, BfrD, and BfrE outer membrane receptor proteins, and although Bordetella pertussis has the bfrD and bfrE genes, the role of these genes in iron uptake has not been demonstrated. In this study, the bfrD and bfrE genes of B. pertussis were shown to be functional in B. bronchiseptica, but neither B. bronchiseptica bfrD nor bfrE imparted catecholamine utilization to B. pertussis. Gene fusion analyses found that expression of B. bronchiseptica bfrA was increased during iron starvation, as is common for iron receptor genes, but that expression of the bfrD and bfrE genes of both species was decreased during iron limitation. As shown previously for B. pertussis, bfrD expression in B. bronchiseptica was also dependent on the BvgAS virulence regulatory system; however, in contrast to the case in B. pertussis, the known modulators nicotinic acid and sulfate, which silence Bvg-activated genes, did not silence expression of bfrD in B. bronchiseptica. Further studies using a B. bronchiseptica bvgAS mutant expressing the B. pertussis bvgAS genes revealed that the interspecies differences in bfrD modulation are partly due to BvgAS differences. Mouse respiratory infection experiments determined that catecholamine utilization contributes to the in vivo fitness of B. bronchiseptica and B. pertussis. Additional evidence of the in vivo importance of the B. pertussis receptors was obtained from serologic studies demonstrating pertussis patient serum reactivity with the B. pertussis BfrD and BfrE proteins.

Effects of acute stress-induced immunomodulation on TH1/TH2 cytokine and catecholamine receptor expression in human peripheral blood cells.

AIMS: There is evidence that psychological stress can modulate immune functions. It has been hypothesized that acute stressors can affect both immune balance (including Th1 and Th2 cytokines) and expression of stress hormone receptors. This study investigated the impact of an acute stressor on gene expressions of glucocorticoid receptor (GR), and ß2-adrenergic receptor (ß2AR) in leukocytes. The effect on T regulatory cells (Treg), regulatory cytokines IL-10 and TGF-ß, Th1 and Th2 cytokines and their receptors IFN-γR and IL-4R was also studied. METHOD: Fourteen normal volunteers completed an acute laboratory stressor, and blood samples were collected before, immediately after, and 1, 2, 6 and 24 h after completion of the tasks. Cytokine production and Treg were determined by flow cytometry. Gene expressions of receptors were analyzed by real-time PCR. RESULTS: IFN-γ was increased immediately and 1 h after stressor (p<0.05, respectively) and upregulation of IFN-γR mRNA was noted at 2, 6 and 24 h (p<0.01, respectively). IL-10 was decreased at 2 h (p<0.01). There were no significant changes in post-task IL-4R, Treg, or TGF-ß. ß2AR mRNA was increased at 2, 6 and 24 h (p<0.01, respectively). On the other hand, no significant alterations were observed in GR expression. CONCLUSION: An acute stressor increased Th1 cytokine production and its receptor expression. ß2AR but not GR was significantly increased after an acute stressor, which supports the hypothesis that catecholamine-mediated signal pathways in communication with the central nervous and immune systems play a fundamental role in acute stress-mediated immune alterations.

Lipopolysaccharide-induced tumor necrosis factor-alpha release is controlled by the central nervous system.

OBJECTIVE: Lipopolysaccharide (LPS) injection in mammals orchestrates the release of many proinflammatory and anti-inflammatory cytokines. Intravenous administration of 0.2 mg/kg of LPS into unanesthetized rats with indwelling jugular catheters provoked a rapid, 50-fold increase in plasma tumor necrosis factor (TNF)-alpha within 30 min, which declined by 60% by 120 min. To test our hypothesis that such a rapid increase of TNF-alpha would be either neurally or hormonally controlled, the effect on TNF-alpha release of anesthesia (ketamine/acepromazine/xylazine) and catecholaminergic agonists and antagonists, either alone or in the presence of LPS, was determined. METHODS: Rats bearing indwelling external jugular catheters were injected with the test drug or saline after removal of 0.6 ml of blood (-10 min). At time zero, LPS or saline was administered. Thereafter, blood samples were drawn at 15, 30, 120, 240 and 360 min. TNF-alpha was measured by immunoassay. RESULTS: Among all the drugs tested, only propranolol increased plasma TNF-alpha. Anesthesia significantly blunted the LPS-induced TNF-alpha peak by 50%. Isoproterenol, a beta-adrenergic agonist, also blocked LPS-induced TNF-alpha release by 70% at 30 min and 90% at 120 min. On the contrary, propranolol, a beta-receptor blocker, induced a highly significant 3-fold increase in plasma TNF-alpha concentrations at 30 min and augmented the response to LPS 2-fold after endotoxin injection. Phentolamine, an alpha-receptor blocker, decreased the LPS-induced TNF-alpha release by 57% at 30 min. Similarly, alpha-bromoergocryptine, a dopamine D2 receptor agonist, decreased the LPS-induced TNF-alpha peak by 70% at 30 min and 50% at 120 min. CONCLUSIONS: We conclude that TNF-alpha is at least in part neurally controlled since the anesthetic blocked its response to LPS. The fact that isoproterenol decreased the LPS-induced TNF-alpha release, whereas propranolol augmented basal and LPS-induced release suggests that the sympathetic nervous system inhibits basal and LPS-stimulated TNF-alpha release via beta-adrenergic receptors. Since phentolamine blocked LPS-induced release, this release may be induced, in part at least, by LPS-stimulated adrenergic drive acting on alpha-adrenergic receptors. The suppressive action of bromoergocryptine, a dopamine D2 receptor agonist, on LPS-induced TNF-alpha release may be mediated in part by suppression of prolactin release, which triggers TNF-alpha release.