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.

Efficient resolution of Pneumocystis murina infection in surfactant protein A-deficient mice following withdrawal of corticosteroid-induced immunosuppression

2006 ◽  
Vol 55 (2) ◽  
pp. 143-147 ◽  
Author(s):  
Michael Linke ◽  
Alan Ashbaugh ◽  
Judith Koch ◽  
Reiko Tanaka ◽  
Peter Walzer
Keyword(s):  
Protein A ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Lung Lavage ◽  
Surfactant Protein A ◽  
Surfactant Protein D ◽  
Wild Type ◽  
Enhanced Expression ◽  
Lymphocyte Populations ◽  
Deficient Mice

Following withdrawal of immunosuppression, surfactant protein A (SP-A)-deficient and wild-type mice cleared Pneumocystis murina infection in a similar manner, but exhibited significant differences in lymphocyte populations, interleukin (IL)-6 levels and chemokine expression levels. A higher percentage of lymphocytes were detected in lung lavage fluid from SP-A-deficient mice, but more CD4+ T cells were isolated from lung tissue of wild-type mice. Higher concentrations of IL-6 were detected in lavage fluid and enhanced expression of lymphotactin and RANTES were detected in the lungs of wild-type mice. Equal levels of surfactant protein D were detected in SP-A-deficient and wild-type mice and no differences were detected in markers of lung injury between the two strains of mice. Thus, SP-A does not enhance organism clearance, but does modulate the host immune response during resolution of P. murina infection.

scholarly journals Surfactant protein D binding to alveolar macrophages

1994 ◽  
Vol 300 (1) ◽  
pp. 237-242 ◽  
Author(s):  
K Miyamura ◽  
L E A Leigh ◽  
J Lu ◽  
J Hopkin ◽  
A López Bernal ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Serum Proteins ◽  
Specific Binding ◽  
Lectin Binding ◽  
Protein A ◽  
Direct Interaction ◽  
Surfactant Protein ◽  
Lung Epithelial Cells ◽  
Surfactant Protein D ◽  
Apparent Dissociation Constant

Surfactant protein D (SP-D) is a lung-specific protein, synthesized and secreted by lung epithelial cells. It belongs to group III of the family of C-type lectins; each member of this group has an unusual overall structure consisting of multiple globular ‘head’ regions (which contain the C-type lectin domains) linked by triple-helical, collagen-like, strands. This group includes the surfactant protein A (SP-A) and the serum proteins mannan-binding protein, conglutinin and collectin-43, all of which have been shown to bind to the C1q receptor found on a wide variety of cells, including macrophages. Both SP-D and SP-A have been shown to enhance oxygen radical production by alveolar macrophages. Although this strongly suggests a direct interaction between SP-D and a specific receptor on alveolar macrophages, it is still unclear whether SP-D binds to the same receptor used by SP-A and/or C1q. Human SP-D was isolated from amniotic fluid and was radiolabelled using 125I. Alveolar macrophages were isolated from human bronchioalveolar lavage fluid, and also from bovine lung washings, by differential adhesion to 24-well tissue-culture plates. The study was carried out using EDTA-containing buffers, to eliminate Ca(2+)-dependent C-type lectin binding, and was also carried out at 4 degrees C to eliminate possible internalization by the cells. 125I-SP-D showed specific binding to alveolar macrophages in both a time- and concentration-saturable manner. The binding was inhibited, by approx. 90%, on addition of a 200-fold excess of unlabelled SP-D. The apparent dissociation constant (Kd) was (3.6 +/- 1.3) x 10(-11) M, based on the assumption that native SP-D is assembled as a dodecamer of 12 identical polypeptides of 43 kDa to yield a protein of 516 kDa. C1q was also shown to bind alveolar macrophages (Kd 3 x 10(-6) M), but addition of C1q did not show inhibition of the binding of 125I-SP-D to the macrophages. We conclude that SP-D binds specifically to alveolar macrophages and the receptor involved is different from that utilized by C1q.

Surfactant metabolism in transgenic mice after granulocyte macrophage-colony stimulating factor ablation

1996 ◽  
Vol 270 (4) ◽  
pp. L650-L658 ◽  
Author(s):  
M. Ikegami ◽  
T. Ueda ◽  
W. Hull ◽  
J. A. Whitsett ◽  
R. C. Mulligan ◽  
...  
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
And Function ◽  
Stimulating Factor ◽  
Deficient Mice ◽  
Surfactant Metabolism

Mice made granulocyte macrophage-colony stimulating factor (GM-CSF)-deficient by homologous recombination maintain normal steady-state hematopoiesis but have an alveolar accumulation of surfactant lipids and protein that is similar to pulmonary alveolar proteinosis in humans. We asked how GM-CSF deficiency alters surfactant metabolism and function in mice. Alveolar and lung tissue saturated phosphatidylcholine (Sat PC) were increased six- to eightfold in 7- to 9-wk-old GM-CSF-deficient mice relative to controls. Incorporation of radiolabeled palmitate and choline into Sat PC was higher in GM-CSF deficient mice than control mice, and no loss of labeled Sat PC occurred from the lungs of GM-CSF-deficient mice. Secretion of radiolabeled Sat PC to the alveolus was similar in GM-CSF-deficient and control mice. Labeled Sat PC and surfactant protein A (SP-A) given by tracheal instillation were cleared rapidly in control mice, but there was no measurable loss from the lungs of GM-CSF-deficient mice. The function of the surfactant from GM-CSF-deficient mice was normal when tested in preterm surfactant-deficient rabbits. GM-CSF deficiency results in a catabolic defect for Sat PC and SP-A.

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.

Clearance of intra-amniotic lung surfactant: uptake and utilization by the fetal rabbit lung

1997 ◽  
Vol 273 (1) ◽  
pp. L55-L63 ◽  
Author(s):  
M. Hallman ◽  
U. Lappalainen ◽  
K. Bry
Keyword(s):  
Amniotic Fluid ◽  
Lung Surfactant ◽  
Protein A ◽  
Alveolar Epithelium ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Lung Compliance ◽  
Rabbit Lung ◽  
Lower Lung ◽  
Lung Surfactant Protein

To investigate the metabolism of intra-amniotic surfactant, surfactant containing double-labeled dipalmitoylphosphatidylcholine (DPPC) was injected in amniotic fluid on days 23-27 of gestation. Within 44 h, DPPC was distributed to the gastrointestinal tract (45.9%), fetal membranes and placenta (8.2%), fetal lung (6.6%), and liver (1.9%). DPPC uptake was higher in the upper than in the lower lung lobes. The mixture of phosphatidylglycerol and DPPC increased the uptake of DPPC that was not saturable (range 15-60 mg phospholipid). There was no detectable metabolism of DPPC taken up by the fetal lung. Surfactant protein A, originating from intra-amniotic heterplogous surfactant, was detected immunohistochemically in alveolar epithelium. Intra-amniotic surfactants did not affect the expression of surfactant protein mRNAs. Intra-amniotic surfactant (1,500-2,000 mg/kg on day 25.3) improved lung compliance of ventilated 27.0-day premature rabbits less than intratracheal surfactant at birth (75-100 mg/kg). Reutilization by the alveolar epithelium of surfactant secreted to future airspaces, airways, and amniotic fluid may be a mechanism that increases intracellular surfactant pool before birth.

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

Complement-mediated host defense in the lung

2000 ◽  
Vol 279 (5) ◽  
pp. L790-L798 ◽  
Author(s):  
Wendy T. Watford ◽  
Andrew J. Ghio ◽  
Jo Rae Wright
Keyword(s):  
Alternative Pathway ◽  
Protein A ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
The Body ◽  
Surfactant Protein D ◽  
Classical Pathway ◽  
Pathway Activity ◽  
Protein Factor ◽  
Pathway Activation

Complement is a system of plasma proteins that aids in the elimination of pathogens from the body. We hypothesized that there is a functional complement system present in the lung that aids in the removal of pathogens. Western blot analysis revealed complement proteins of the alternative and classical pathways of complement in bronchoalveolar lavage fluids (BALF) from healthy volunteers. Functional classical pathway activity was detected in human BALF, but there was no significant alternative pathway activity in lavage fluid, a finding that correlates with the low level of the alternative pathway protein, factor B, in these samples. Although the classical pathway of complement was functional in lavage fluid, the level of the classical pathway activator C1q was very low. We tested the ability of the lung- specific surfactant proteins, surfactant protein A (SP-A) and surfactant protein D (SP-D), to substitute for C1q in classical pathway activation, since they have structural homology to C1q. However, neither SP-A nor SP-D restored classical pathway activity to C1q-depleted serum. These data suggest that the classical pathway of complement is functionally active in the lung where it may play a role in the recognition and clearance of bacteria.

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.

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