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 Pathway to lamellar bodies for surfactant protein A

2010 ◽  
Vol 299 (1) ◽  
pp. L51-L58 ◽  
Author(s):  
Aron B. Fisher ◽  
Chandra Dodia ◽  
Peter Ruckert ◽  
Jian-Qin Tao ◽  
Sandra R. Bates
Keyword(s):  
Specific Activity ◽  
Protein A ◽  
Lamellar Body ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Lung Lavage ◽  
Surfactant Protein A ◽  
Coated Vesicle ◽  
Lamellar Bodies ◽  
Vesicle Budding

Alveolar surfactant protein A (SP-A) is endocytosed by type II epithelial cells through clathrin-dependent uptake and targeted to lamellar bodies for resecretion. However, the mechanism for secretion of newly synthesized SP-A, whether regulated exocytosis of lamellar bodies or constitutive secretion, is unresolved. If it is the latter, lamellar body SP-A would represent endocytosed protein. Amantadine, an inhibitor of clathrin-coated vesicle budding, was used to evaluate the role of endocytosis in accumulation of SP-A in lamellar bodies. In isolated rat lungs, amantadine (10 mM) inhibited uptake of endotracheally instilled 35S-labeled biosynthesized surfactant proteins by >80%. To study trafficking of newly synthesized SP-A, lungs were perfused for up to 6 h with [35S]methionine, and surfactant was isolated from lung lavage fluid and lamellar bodies were isolated from lung homogenate. With control lungs, the mean specific activity of [35S]SP-A (disintegrations per minute per microgram of SP-A) increased linearly with time of perfusion: it was significantly higher in isolated lamellar bodies than in surfactant and was increased in both compartments by 50–60% in the presence of 0.1 mM 8-bromo-cAMP. These results suggest a precursor-product relationship between lamellar body and extracellular [35S]SP-A. Specific activities in both compartments were unaffected by addition of amantadine (10 mM) to the lung perfusate, indicating that uptake from the alveolar space was not responsible for the increase in lamellar body [35S]SP-A. Thus the pathway for secretion of newly synthesized SP-A is by transfer from the site of synthesis to the storage/secretory organelle prior to lamellar body exocytosis.

scholarly journals Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lidan Liu ◽  
Chaim Z. Aron ◽  
Cullen M. Grable ◽  
Adrian Robles ◽  
Xiangli Liu ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
Inflammatory Cytokine ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Mrna Levels ◽  
Wild Type ◽  
Cytokine Mrna ◽  
Protein Levels ◽  
Cytokine Levels

AbstractLevels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A−/−) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A−/− mice compared to wild type mice. Gavage of neonatal SP-A−/− mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A−/− mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.

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.

SURFACTANT PROTEIN A IN BRONCHOALVEOLAR LAVAGE FLUID OF CHILDREN WITH CYSTIC FIBROSIS

2004 ◽  
Vol 32 (Supplement) ◽  
pp. A115
Author(s):  
Neal J Thomas ◽  
Gavin R Graff ◽  
Todd M Umstead ◽  
David S Phelps ◽  
Joanna Floros
Keyword(s):  
Cystic Fibrosis ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Protein A ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Surfactant Protein A

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.

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