scholarly journals Effector mechanisms responsible for gamma interferon-mediated host resistance to Legionella pneumophila lung infection: the role of endogenous nitric oxide differs in susceptible and resistant murine hosts.

1996 ◽  
Vol 64 (12) ◽  
pp. 5151-5160 ◽  
Author(s):  
L Heath ◽  
C Chrisp ◽  
G Huffnagle ◽  
M LeGendre ◽  
Y Osawa ◽  
...  
2000 ◽  
Vol 68 (12) ◽  
pp. 6567-6573 ◽  
Author(s):  
Joan K. Brieland ◽  
Craig Jackson ◽  
Steve Hurst ◽  
David Loebenberg ◽  
Tony Muchamuel ◽  
...  

ABSTRACT The in vivo role of endogenous interleukin-18 (IL-18) in modulating gamma interferon (IFN-γ)-mediated resolution of replicativeLegionella pneumophila lung infection was assessed using a murine model of Legionnaires' disease. Intratracheal inoculation of A/J mice with virulent bacteria (106 L. pneumophila organisms per mouse) resulted in induction of IL-18 protein in bronchoalveolar lavage fluid (BALF) and intrapulmonary expression of IL-18 mRNA. Real-time quantitative RT-PCR analysis of infected lung tissue demonstrated that induction of IL-18 in BALF preceded induction of IL-12 and IFN-γ mRNAs in the lung. Blocking intrapulmonary IL-18 activity by administration of a monoclonal antibody (MAb) to the IL-18 receptor (anti-IL-18R MAb) prior toL. pneumophila infection inhibited induction of intrapulmonary IFN-γ production but did not significantly alter resolution of replicative L. pneumophila lung infection. In contrast, blocking endogenous IL-12 activity by administration of anti-IL-12 MAb) alone or in combination with anti-IL-18R MAb inhibited induction of intrapulmonary IFN-γ and resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection. Taken together, these results demonstrate that IL-18 plays a key role in modulating induction of IFN-γ in the lung in response to L. pneumophila and that together with IL-12, IL-18 regulates intrapulmonary growth of the bacteria.


Life Sciences ◽  
2007 ◽  
Vol 80 (4) ◽  
pp. 329-336 ◽  
Author(s):  
Koji Takeuchi ◽  
Ryo Hatazawa ◽  
Mayu Tanigami ◽  
Akiko Tanaka ◽  
Ryoko Ohno ◽  
...  

2020 ◽  
Vol 22 (1) ◽  
pp. 72-79
Author(s):  
Alexandra Lee ◽  
◽  
Warwick Butt ◽  
◽  
◽  
...  

Inhaled nitric oxide has been used for 30 years to improve oxygenation and decrease pulmonary vascular resistance. In the past 15 years, there has been increased understanding of the role of endogenous nitric oxide on cell surface receptors, mitochondria, and intracellular processes involving calcium and superoxide radicals. This has led to several animal and human experiments revealing a potential role for administered nitric oxide or nitric oxide donors in patients with systemic inflammatory response syndrome or ischaemia–reperfusion injury, and in patients for whom exposure of blood to artificial surfaces has occurred.


1990 ◽  
Vol 258 (4) ◽  
pp. H1250-H1254 ◽  
Author(s):  
A. Chu ◽  
D. E. Chambers ◽  
C. C. Lin ◽  
W. D. Kuehl ◽  
F. R. Cobb

This study evaluates the role of endogenous nitric oxide in the modulation of basal coronary vasomotor tone by studying the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide formation from L-arginine, on resting epicardial coronary diameter and coronary flow. L-NMMA (5 mg/kg) was infused in seven awake dogs chronically instrumented with coronary dimension crystals for measurement of epicardial coronary diameter, and Doppler flow probes for quantitation of phasic coronary flow (vasomotion of distal regulatory resistance coronary vessels). Epicardial coronary diameter decreased 5.5% from 3.47 +/- 0.17 to 3.28 +/- 0.15 mm (mean +/- SE). The diameter change was gradual, reaching a maximum at 13 +/- 2 min after infusion, and persistent, lasting greater than 90 min. Phasic coronary flow did not change. Mean aortic pressure significantly increased from 99 +/- 3 to 111 +/- 3 mmHg and heart rate decreased from 56 +/- 4 to 46 +/- 3 beats/min. Left ventricular end-diastolic pressure and contractility were not significantly altered. L-Arginine (66 mg/kg) but not D-arginine reversed all hemodynamic parameters. These data support an important role of nitric oxide in modulating basal epicardial coronary vasomotor tone and systemic vascular resistance.


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