scholarly journals Selective Inhibition of Inducible NO Synthase Activity In Vivo Reverses Inflammatory Abnormalities in Surfactant Protein D-Deficient Mice

2007 ◽  
Vol 179 (12) ◽  
pp. 8090-8097 ◽  
Author(s):  
Elena N. Atochina-Vasserman ◽  
Michael F. Beers ◽  
Helchem Kadire ◽  
Yaniv Tomer ◽  
Adam Inch ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Surfactant Protein ◽  
No Synthase ◽  
Surfactant Protein D ◽  
Inducible No Synthase ◽  
Deficient Mice

Toxic dilatation of colon in a rat model of colitis is linked to an inducible form of nitric oxide synthase

1996 ◽  
Vol 270 (3) ◽  
pp. G425-G430 ◽  
Author(s):  
M. Mourelle ◽  
J. Vilaseca ◽  
F. Guarner ◽  
A. Salas ◽  
J. R. Malagelada
Keyword(s):  
Nitric Oxide ◽  
Selective Inhibition ◽  
No Synthase ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Toxic Dilatation ◽  
Inducible No Synthase ◽  
And Control

The contribution of nitric oxide (NO) to the altered colonic contractility of acute colitis was investigated in the 2,4,6-trinitroben-zenesulfonic acid model. NO synthase was measured in colonic tissue; the effects of NO synthase inhibition on colonic contractility were studied in vitro and in vivo. Inducible NO synthase was not detected in normal colons, whereas inflamed colons showed high activity. Acute inflammation was associated with enlarged colonic perimeter. NO synthase inhibitors or selective inhibitors of the inducible enzyme prevented colonic dilatation. In vitro, contractile responses to KCl were lower in muscle from colitic than control rats. After NO synthase inhibition, however, no difference was observed between colitic and control muscle contractility. In vivo, intracolonic pressure was lower in colitic than in control rats. Selective inhibition of inducible NO synthase increased intracolonic pressure in colitic but not in control rats. In conclusion, NO generation by inducible enzymes impairs smooth muscle contractility in colitis and may be involved in the pathogenesis of toxic dilatation of the colon.

Surfactant metabolism in surfactant protein A-deficient mice

1997 ◽  
Vol 272 (3) ◽  
pp. L479-L485 ◽  
Author(s):  
M. Ikegami ◽  
T. R. Korfhagen ◽  
M. D. Bruno ◽  
J. A. Whitsett ◽  
A. H. Jobe
Keyword(s):  
Lung Tissue ◽  
Protein A ◽  
Surfactant Protein ◽  
Normal Lung ◽  
Tissue Slices ◽  
Normal Lung Function ◽  
Deficient Mice ◽  
Surfactant Metabolism

In the present study we asked if surfactant metabolism was altered in surfactant protein (SP) A-deficient mice in vivo. Although previous studies in vitro demonstrated that SP-A modulates surfactant secretion and reuptake by type II cells, mice made SP-A deficient by homologous recombination grow and reproduce normally and have normal lung function. Alveolar and lung tissue saturated phophatidylcholine (Sat PC) pools were 50 and 26% larger, respectively, in SP-A(-/-) mice than in SP-A(+/+) mice. Radiolabeled choline and palmitate incorporation into lung Sat PC was similar both in vivo and for lung tissue slices in vitro from SP-A(+/+) and SP-A(-/-) mice. Percent secretion of radiolabeled Sat PC was unchanged from 3 to 15 h, although SP-A(-/-) mice retained more labeled Sat PC in the alveolar lavages at 48 h (consistent with the increased surfactant pool sizes). Clearance of radiolabeled dipalmitoylphosphatidylcholine and SP-B from the air spaces after intratracheal injection was similar in SP-A(-/-) and SP-A(+/+) mice. Lack of SP-A had minimal effects on the overall metabolism of Sat PC or SP-B in mice.

scholarly journals Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis

2017 ◽  
Vol 114 (38) ◽  
pp. 10178-10183 ◽  
Author(s):  
Hana Sarashina-Kida ◽  
Hideo Negishi ◽  
Junko Nishio ◽  
Wataru Suda ◽  
Yuki Nakajima ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Local Environment ◽  
Surfactant Protein ◽  
Commensal Bacteria ◽  
Intestinal Lumen ◽  
Surfactant Protein D ◽  
Organ Systems ◽  
Notable Increase ◽  
Health And Disease ◽  
Deficient Mice

The commensal microbiota within the gastrointestinal tract is essential in maintaining homeostasis. Indeed, dysregulation in the repertoire of microbiota can result in the development of intestinal immune–inflammatory diseases. Further, this immune regulation by gut microbiota is important systemically, impacting health and disease of organ systems beyond the local environment of the gut. What has not been explored is how distant organs might in turn shape the microbiota via microbe-targeted molecules. Here, we provide evidence that surfactant protein D (SP-D) synthesized in the gallbladder and delivered into intestinal lumen binds selectively to species of gut commensal bacteria. SP-D–deficient mice manifest intestinal dysbiosis and show a susceptibility to dextran sulfate sodium-induced colitis. Further, fecal transfer from SP-D–deficient mice to wild-type, germ-free mice conveyed colitis susceptibility. Interestingly, colitis caused a notable increase inSftpdgene expression in the gallbladder, but not in the lung, via the activity of glucocorticoids produced in the liver. These findings describe a unique mechanism of interorgan regulation of intestinal immune homeostasis by SP-D with potential clinical implications such as cholecystectomy.

scholarly journals Sevoflurane Promotes Bactericidal Properties of Macrophages through Enhanced Inducible Nitric Oxide Synthase Expression in Male Mice

2019 ◽  
Vol 131 (6) ◽  
pp. 1301-1315 ◽  
Author(s):  
Thomas J. Gerber ◽  
Valérie C. O. Fehr ◽  
Suellen D. S. Oliveira ◽  
Guochang Hu ◽  
Randal Dull ◽  
...  
Keyword(s):  
Early Stage ◽  
No Synthase ◽  
Control Group ◽  
Male Mice ◽  
Proinflammatory Response ◽  
E Coli ◽  
Inducible No Synthase ◽  
Bactericidal Properties

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties. Methods Murine bone marrow–derived macrophages were stimulated in vitro with lipopolysaccharide in the presence and absence of 2% sevoflurane. Expression of cytokines and inducible NO synthase as well as uptake of fluorescently labeled Escherichia coli (E. coli) were measured. The in vivo endotoxemia model consisted of an intraperitoneal lipopolysaccharide injection after anesthesia with either ketamine and xylazine or 4% sevoflurane. Male mice (n = 6 per group) were observed for a total of 20 h. During the last 30 min fluorescently labeled E. coli were intraperitoneally injected. Peritoneal cells were extracted by peritoneal lavage and inducible NO synthase expression as well as E. coli uptake by peritoneal macrophages was determined using flow cytometry. Results In vitro, sevoflurane enhanced lipopolysaccharide-induced inducible NO synthase expression after 8 h by 466% and increased macrophage uptake of fluorescently labeled E. coli by 70% compared with vehicle-treated controls. Inhibiting inducible NO synthase expression pharmacologically abolished this increase in bacteria uptake. In vivo, inducible NO synthase expression was increased by 669% and phagocytosis of E. coli by 49% compared with the control group. Conclusions Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase–dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia.

Pulmonary dysfunction in neonatal SP-B-deficient mice

1997 ◽  
Vol 273 (4) ◽  
pp. L875-L882 ◽  
Author(s):  
Keisuke Tokieda ◽  
Jeffrey A. Whitsett ◽  
Jean C. Clark ◽  
Timothy E. Weaver ◽  
Kazushige Ikeda ◽  
...  
Keyword(s):  
Critical Role ◽  
Protein A ◽  
Surfactant Protein ◽  
Lung Compliance ◽  
Phospholipid Content ◽  
Surfactant Protein D ◽  
Intratracheal Administration ◽  
Lung Expansion ◽  
B Mice ◽  
Deficient Mice

Pulmonary function was assessed in newborn wild-type and homozygous and heterozygous surfactant protein B (SP-B)-deficient mice after birth. SP-B+/+ and SP-B+/− mice became well oxygenated and survived postnatally. Although lung compliance was decreased slightly in the SP-B+/− mice, lung volumes and compliances were decreased markedly in homozygous SP-B−/− mice. They died rapidly after birth, failing to inflate their lungs or oxygenate. SP-B proprotein was absent in the SP-B−/− mice and was reduced in the SP-B+/− mice, as assessed by Western analysis. Surfactant protein A, surfactant proprotein C, surfactant protein D, and surfactant phospholipid content in lungs from SP-B+/− and SP-B−/− mice were not altered. Lung saturated phosphatidylcholine and precursor incorporation into saturated phosphatidylcholine were not influenced by SP-B genotype. Intratracheal administration of perfluorocarbon resulted in lung expansion, oxygenation, and prolonged survival of SP-B−/− mice and in reduced lung compliance in SP-B+/+ and SP-B+/− mice. Lack of SP-B caused respiratory failure at birth, and decreased SP-B protein was associated with reduced lung compliance. These findings demonstrate the critical role of SP-B in perinatal adaptation to air breathing.

scholarly journals Surfactant protein A and surfactant protein D in health and disease

1998 ◽  
Vol 275 (1) ◽  
pp. L1-L13 ◽  
Author(s):  
Robert J. Mason ◽  
Kelly Greene ◽  
Dennis R. Voelker
Keyword(s):  
Host Defense ◽  
Wide Spectrum ◽  
Protein A ◽  
Three Dimensional ◽  
Surfactant Protein ◽  
Systemic Circulation ◽  
Surfactant Protein D ◽  
Phagocytic Cells ◽  
Surfactant System

Surfactant protein (SP) A and SP-D are collagenous glycoproteins with multiple functions in the lung. Both of these proteins are calcium-dependent lectins and are structurally similar to mannose-binding protein and bovine conglutinin. Both form polyvalent multimeric structures for interactions with pathogens, cells, or other molecules. SP-A is an integral part of the surfactant system, binds phospholipids avidly, and is found in lamellar bodies and tubular myelin. Initially, most research interest focused on its role in surfactant homeostasis. Recently, more attention has been placed on the role of SP-A as a host defense molecule and its interactions with pathogens and phagocytic cells. SP-D is much less involved with the surfactant system. SP-D appears to be primarily a host defense molecule that binds surfactant phospholipids poorly and is not found in lamellar inclusion bodies or tubular myelin. Both SP-A and SP-D bind a wide spectrum of pathogens including viruses, bacteria, fungi, and pneumocystis. In addition, both molecules have been measured in the systemic circulation by immunologic methods and may be useful biomarkers of disease. The current challenges are characterization of the three-dimensional crystal structure of SP-A and SP-D, molecular cloning of their receptors, and determination of their precise physiological functions in vivo.

scholarly journals Clearance of Pseudomonas aeruginosa from a Healthy Ocular Surface Involves Surfactant Protein D and Is Compromised by Bacterial Elastase in a Murine Null-Infection Model

2009 ◽  
Vol 77 (6) ◽  
pp. 2392-2398 ◽  
Author(s):  
James J. Mun ◽  
Connie Tam ◽  
David Kowbel ◽  
Samuel Hawgood ◽  
Mitchell J. Barnett ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Ocular Surface ◽  
Surfactant Protein ◽  
Tear Fluid ◽  
Bacterial Invasion ◽  
Surfactant Protein D ◽  
Infection Model ◽  
Strain Pao1 ◽  
Corneal Epithelial

ABSTRACT Our previous studies showed that surfactant protein D (SP-D) is present in human tear fluid and that it can protect corneal epithelial cells against bacterial invasion. Here we developed a novel null-infection model to test the hypothesis that SP-D contributes to the clearance of viable Pseudomonas aeruginosa from the healthy ocular surface in vivo. Healthy corneas of Black Swiss mice were inoculated with 107 or 109 CFU of invasive (PAO1) or cytotoxic (6206) P. aeruginosa. Viable counts were performed on tear fluid collected at time points ranging from 3 to 14 h postinoculation. Healthy ocular surfaces cleared both P. aeruginosa strains efficiently, even when 109 CFU was used: e.g., <0.01% of the original inoculum was recoverable after 3 h. Preexposure of eyes to bacteria did not enhance clearance. Clearance of strain 6206 (low protease producer), but not strain PAO1 (high protease producer), was delayed in SP-D gene-targeted (SP-D−/−) knockout mice. A protease mutant of PAO1 (PAO1 lasA lasB aprA) was cleared more efficiently than wild-type PAO1, but this difference was negligible in SP-D−/− mice, which were less able to clear the protease mutant. Experiments to study mechanisms for these differences revealed that purified elastase could degrade tear fluid SP-D in vivo. Together, these data show that SP-D can contribute to the clearance of P. aeruginosa from the healthy ocular surface and that proteases can compromise that clearance. The data also suggest that SP-D degradation in vivo is a mechanism by which P. aeruginosa proteases could contribute to virulence.

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