Inhaled nitric oxide injures the pulmonary surfactant system of lambs in vivo

1996 ◽  
Vol 270 (2) ◽  
pp. L273-L280 ◽  
Author(s):  
S. Matalon ◽  
V. DeMarco ◽  
I. Y. Haddad ◽  
C. Myles ◽  
J. W. Skimming ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bronchoalveolar Lavage ◽  
Surface Properties ◽  
Pulmonary Surfactant ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant System ◽  
Minimum Surface Tension

Nitric oxide (.NO) is a free radical, and as such may damage the pulmonary surfactant system. To determine the potential toxicity of .NO in vivo, we exposed 35 newborn lambs to 0, 20, 80 or 200 ppm .NO in either 21 or 60% O2 for 6 h. At the end of the exposure, lambs had normal values of arterial Po2, Pco2, and pH; total protein concentration in the bronchoalveolar lavage was also at normal levels. There were no differences in the surface properties of surfactant among the air or 60% O2 groups. Pulmonary surfactant samples, isolated from the bronchoalveolar lavage of lambs breathing air or 20 ppm .NO and reconstituted at a lipid concentration of 3 mg/ml, reached a low minimum surface tension (Tmin < 3 mN/m) in a pulsating bubble surfactometer. On the other hand, abnormal surface properties were observed in 36 and 60% of surfactant samples isolated from lungs of lambs that breathed 80 or 200 ppm .NO, respectively. These findings were confirmed using a captive bubble surfactometer. Surfactant protein A, isolated from the lungs of lambs that breathed 200 ppm .NO, exhibited decreased ability to aggregate lipids in vitro. These data are consistent with injury to the surfactant apoproteins during inhalation of either 80 or 200 ppm .NO for 6 h.

Surfactant protein A regulates surfactant phospholipid clearance after LPS-induced injury in vivo

2002 ◽  
Vol 283 (1) ◽  
pp. L76-L85 ◽  
Author(s):  
Omar A. Quintero ◽  
Thomas R. Korfhagen ◽  
Jo Rae Wright
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Surfactant ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Wild Type ◽  
Surfactant Phospholipids

Previous in vitro studies have suggested that surfactant protein A (SP-A) may play a role in pulmonary surfactant homeostasis by mediating surfactant secretion and clearance. However, mice made deficient in SP-A [SP-A (−/−) animals] have relatively normal levels of surfactant compared with wild-type SP-A (+/+) animals. We hypothesize that SP-A may play a role in surfactant homeostasis after acute lung injury. Bacterial lipopolysaccharide was instilled into the lungs of SP-A (−/−) mice and SP-A (+/+) mice to induce injury. Surfactant phospholipid levels were increased 1.6-fold in injured SP-A (−/−) animals, although injury did not alter [3H]choline or [14C]palmitate incorporation into dipalmitoylphosphatidylcholine (DPPC), suggesting no change in surfactant synthesis/secretion 12 h after injury. Clearance of [3H]DPPC from the lungs of injured SP-A (−/−) animals was decreased by ∼40%. Instillation of 50 μg of exogenous SP-A rescued both the clearance defect and the increased phospholipid defect in injured SP-A (−/−) animals, suggesting that SP-A may play a role in regulating clearance of surfactant phospholipids after acute lung injury.

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.

Exposure of surfactant protein A to ozone in vitro and in vivo impairs its interactions with alveolar cells

1992 ◽  
Vol 262 (1) ◽  
pp. L63-L68 ◽  
Author(s):  
R. S. Oosting ◽  
J. F. Van Iwaarden ◽  
L. Van Bree ◽  
J. Verhoef ◽  
L. M. Van Golde ◽  
...  
Keyword(s):  
Superoxide Anion ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Alveolar Type ◽  
Type Ii ◽  
Superoxide Anion Production ◽  
Anion Production

This study focused on the question of whether exposure of surfactant protein A (SP-A) to ozone affected properties of this protein that may be involved in regulating alveolar type II cell and alveolar macrophage functions. In vitro exposure of human or canine SP-A to ozone reduced the ability of this protein to inhibit phorbol-ester induced secretion of [3H]phosphatidylcholine by alveolar type II cells in culture. Ozone-exposed human SP-A showed a decreased ability to enhance phagocytosis of herpes simplex virus and to stimulate superoxide anion production by alveolar macrophages. Experiments with elastase showed that ozone-exposed canine SP-A was more susceptible to proteolysis. A conformational change of the protein could underlie this phenomenon. Surfactant isolated from ozone-exposed rats (0.4 ppm ozone for 12 h) was also less able to stimulate superoxide anion production by alveolar macrophages than surfactant from control rats, which suggested that SP-A in vivo was also susceptible to ozone. The results of this study suggest that SP-A-alveolar cell interactions can be inhibited by ozone exposure, which may contribute to the toxicity of ozone in the lungs.

Alterations in the surface properties of lung surfactant in the torpid marsupial Sminthopsis crassicaudata

1998 ◽  
Vol 84 (1) ◽  
pp. 146-156 ◽  
Author(s):  
Olga V. Lopatko ◽  
Sandra Orgeig ◽  
Christopher B. Daniels ◽  
David Palmer
Keyword(s):  
Surface Tension ◽  
Surface Properties ◽  
Surface Activity ◽  
Pulmonary Surfactant ◽  
Lung Surfactant ◽  
Lung Compliance ◽  
Equilibrium Surface Tension ◽  
Sminthopsis Crassicaudata

Lopatko, Olga V., Sandra Orgeig, Christopher B. Daniels, and David Palmer. Alterations in the surface properties of lung surfactant in the torpid marsupial Sminthopsis crassicaudata. J. Appl. Physiol. 84(1): 146–156, 1998.—Torpor changes the composition of pulmonary surfactant (PS) in the dunnart Sminthopsis crassicaudata [C. Langman, S. Orgeig, and C. B. Daniels. Am. J. Physiol. 271 ( Regulatory Integrative Comp. Physiol. 40): R437–R445, 1996]. Here we investigated the surface activity of PS in vitro. Five micrograms of phospholipid per centimeter squared surface area of whole lavage (from mice or from warm-active, 4-, or 8-h torpid dunnarts) were applied dropwise onto the subphase of a Wilhelmy-Langmuir balance at 20°C and stabilized for 20 min. After 4 h of torpor, the adsorption rate increased, and equilibrium surface tension (STeq), minimal surface tension (STmin), and the %area compression required to achieve STmin decreased, compared with the warm-active group. After 8 h of torpor, STmin decreased [from 5.2 ± 0.3 to 4.1 ± 0.3 (SE) mN/m]; %area compression required to achieve STmindecreased (from 43.4 ± 1.0 to 27.4 ± 0.8); the rate of adsorption decreased; and STeqincreased (from 26.3 ± 0.5 to 38.6 ± 1.3 mN/m). ST-area isotherms of warm-active dunnarts and mice at 20°C had a shoulder on compression and a plateau on expansion. These disappeared on the isotherms of torpid dunnarts. Samples of whole lavage (from warm-active and 8-h torpor groups) containing 100 μg phospholipid/ml were studied by using a captive-bubble surfactometer at 37°C. After 8 h of torpor, STmin increased (from 6.4 ± 0.3 to 9.1 ± 0.3 mN/m) and %area compression decreased in the 2nd (from 88.6 ± 1.7 to 82.1 ± 2.0) and 3rd (from 89.1 ± 0.8 to 84.9 ± 1.8) compression-expansion cycles, compared with warm-active dunnarts. ST-area isotherms of warm-active dunnarts at 37°C did not have a shoulder on compression. This shoulder appeared on the isotherms of torpid dunnarts. In conclusion, there is a strong correlation between in vitro changes in surface activity and in vivo changes in lipid composition of PS during torpor, although static lung compliance remained unchanged (see Langman et al. cited above). Surfactant from torpid animals is more active at 20°C and less active at 37°C than that of warm-active animals, which may represent a respiratory adaptation to low body temperatures of torpid dunnarts.

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 Surfactant Protein D Increases Phagocytosis of Hypocapsular Cryptococcus neoformans by Murine Macrophages and Enhances Fungal Survival

2009 ◽  
Vol 77 (7) ◽  
pp. 2783-2794 ◽  
Author(s):  
Scarlett Geunes-Boyer ◽  
Timothy N. Oliver ◽  
Guilhem Janbon ◽  
Jennifer K. Lodge ◽  
Joseph Heitman ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Defense Mechanisms ◽  
Protein A ◽  
Surfactant Protein ◽  
Immune Defense ◽  
Surfactant Protein D ◽  
Wild Type ◽  
Phagocytic Cells

ABSTRACT Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a protective cellular immune response, the inhalation of C. neoformans cells or spores results in pulmonary infection. C. neoformans cells produce a polysaccharide capsule composed predominantly of glucuronoxylomannan, which constitutes approximately 90% of the capsular material. In the lungs, surfactant protein A (SP-A) and SP-D contribute to immune defense by facilitating the aggregation, uptake, and killing of many microorganisms by phagocytic cells. We hypothesized that SP-D plays a role in C. neoformans pathogenesis by binding to and enhancing the phagocytosis of the yeast. Here, the abilities of SP-D to bind to and facilitate the phagocytosis and survival of the wild-type encapsulated strain H99 and the cap59Δ mutant hypocapsular strain are assessed. SP-D binding to cap59Δ mutant cells was approximately sixfold greater than binding to wild-type cells. SP-D enhanced the phagocytosis of cap59Δ cells by approximately fourfold in vitro. To investigate SP-D binding in vivo, SP-D−/− mice were intranasally inoculated with Alexa Fluor 488-labeled cap59Δ or H99 cells. By confocal microscopy, a greater number of phagocytosed C. neoformans cells in wild-type mice than in SP-D−/− mice was observed, consistent with in vitro data. Interestingly, SP-D protected C. neoformans cells against macrophage-mediated defense mechanisms in vitro, as demonstrated by an analysis of fungal viability using a CFU assay. These findings provide evidence that C. neoformans subverts host defense mechanisms involving surfactant, establishing a novel virulence paradigm that may be targeted for therapy.

Inhaled nitric oxide increases surfactant protein gene expression in the intact lamb

2003 ◽  
Vol 285 (3) ◽  
pp. L628-L633 ◽  
Author(s):  
Regan B. Stuart ◽  
Boaz Ovadia ◽  
Vincent V. Suzara ◽  
Patrick A. Ross ◽  
Stephan Thelitz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Dna Content ◽  
Protein Gene ◽  
Surfactant Protein ◽  
Inhaled Nitric Oxide ◽  
Mrna Content ◽  
Lung Biopsies

Inhaled nitric oxide (iNO) is used to treat a number of disease processes. Although in vitro data suggest that nitric oxide (NO) alters surfactant protein gene expression, the effects in vivo have not been studied. The objective of this study was to evaluate the effects of iNO on surfactant protein (SP)-A, -B, and -C gene expression in the intact lamb. Thirteen 4-wk-old lambs were mechanically ventilated with 21% oxygen and received iNO at 40 ppm ( n = 7) or vehicle gas ( n = 6) for 24 h. Peripheral lung biopsies were obtained at 0, 12, and 24 h and analyzed for surfactant mRNA, protein, and total DNA content. Inhaled NO increased SP-A and SP-B mRNA content by 80% from 0 to 12 h and by 78 and 71%, respectively, from 0 to 24 h. There was an increase in SP-A and SP-B protein content by 45% from 0 to 12 h, and a decrease by 70 and 65%, respectively, from 0 to 24 h. DNA content was unchanged. The mechanisms and physiological effects of these findings warrant further investigation.

scholarly journals Surfactant Protein A Modulates the Inflammatory Response in Macrophages during Tuberculosis

2004 ◽  
Vol 72 (2) ◽  
pp. 645-650 ◽  
Author(s):  
Jeffrey A. Gold ◽  
Yoshihiko Hoshino ◽  
Naohiko Tanaka ◽  
William N. Rom ◽  
Bindu Raju ◽  
...  
Keyword(s):  
Protein A ◽  
Mycobacterial Infection ◽  
Surfactant Protein ◽  
In Vitro Models ◽  
Dominant Negative ◽  
Surfactant Protein A ◽  
Low Concentrations ◽  
Hiv 1

ABSTRACT Tuberculosis leads to immune activation and increased human immunodeficiency virus type 1 (HIV-1) replication in the lung. However, in vitro models of mycobacterial infection of human macrophages do not fully reproduce these in vivo observations, suggesting that there are additional host factors. Surfactant protein A (SP-A) is an important mediator of innate immunity in the lung. SP-A levels were assayed in the human lung by using bronchoalveolar lavage (BAL). There was a threefold reduction in SP-A levels during tuberculosis only in the radiographically involved lung segments, and the levels returned to normal after 1 month of treatment. The SP-A levels were inversely correlated with the percentage of neutrophils in BAL fluid, suggesting that low SP-A levels were associated with increased inflammation in the lung. Differentiated THP-1 macrophages were used to test the effect of decreasing SP-A levels on immune function. In the absence of infection with Mycobacterium tuberculosis, SP-A at doses ranging from 5 to 0.01 μg/ml inhibited both interleukin-6 (IL-6) production and HIV-1 long terminal repeat (LTR) activity. In macrophages infected with M. tuberculosis, SP-A augmented both IL-6 production and HIV-1 LTR activity. To better understand the effect of SP-A, we measured expression of CAAT/enhancer binding protein beta (C/EBPβ), a transcription factor central to the regulation of IL-6 and the HIV-1 LTR. In macrophages infected with M. tuberculosis, SP-A reduced expression of a dominant negative isoform of C/EBPβ. These data suggest that SP-A has pleiotropic effects even at the low concentrations found in tuberculosis patients. This protein augments inflammation in the presence of infection and inhibits inflammation in uninfected macrophages, protecting uninvolved lung segments from the deleterious effects of inflammation.

A Synthetic Segment of Surfactant Protein A: Structure, in Vitro Surface Activity, and in Vivo Efficacy

1996 ◽  
Vol 39 (6) ◽  
pp. 938-946 ◽  
Author(s):  
Frans J Walther ◽  
Remedios David-Cu ◽  
Carol Leung ◽  
Roberta Bruni ◽  
José Hernández-Juviel ◽  
...  
Keyword(s):  
Surface Activity ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
In Vivo Efficacy
Sign in / Sign up

Export Citation Format

Share Document