Surfactant Protein-a but Not Sp-D Deficient Mice Are Susceptible to Bacterial Infection in the Lung

LeVine, Ann Marie; Gwozdz, Jodie; Fisher, James H.; Whitsett, Jeffrey A.; Korfhagen, Thomas R.

doi:10.1097/00003246-199912001-00317

Cited by 47 publications

(63 citation statements)

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“…In SP-A null mice, exposure to pathogens, including viruses, results in increased neutrophilia, epithelial injury and persistence of infection compared with control mice, indicating a protective role for surfactant proteins in lung defence. 44 In this study, levels of SP-A were increased in subjects with eosinophilic and neutrophilic asthma compared with controls, indicating host-defence activity in these subjects. SP-A did not seem to be a specific marker of innate immune activation as levels were similar between the asthma subtypes.…”

Section: Discussionsupporting

confidence: 49%

Innate immune activation in neutrophilic asthma and bronchiectasis

Simpson

Grissell

Douwes

et al. 2007

Thorax

291

288

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Background: The role of the innate immune system in the pathogenesis of asthma is unclear. Activation of innate immune receptors in response to bacterial lipopolysaccharide, viral infection and particulate matter triggers a pre-programmed inflammatory response, which involves interleukin (IL)8 and neutrophil influx. The inflammatory response in asthma is heterogeneous. Aim: To test the hypothesis that innate immune activation may be a relevant inflammatory mechanism in neutrophilic asthma where IL8 levels are increased. Methods: Induced sputum was obtained from non-smoking adults with asthma (n = 49), healthy controls (n = 13) and a positive reference group with bronchiectasis (n = 9). Subjects with asthma were classified into inflammatory subtypes using induced sputum cell counts. Sputum was examined for mRNA expression of the innate immune receptors toll-like receptor (TLR)2, TLR4 and CD14, and inflammatory cytokines. A separate sputum portion was dispersed and the supernatant assayed for surfactant protein A, IL8, soluble CD14 and endotoxin. Results: Expression of innate immune receptors was increased in subjects with bronchiectasis and neutrophilic asthma compared with other asthma subtypes and controls. Increased expression of the receptors TLR2, TLR4 and CD14, as well as the pro-inflammatory cytokines IL8 and IL1b, was observed. Subjects with neutrophilic asthma had higher airway levels of endotoxin than the other groups studied. Conclusion: There is evidence of activation of the innate immune system in asthma which results in the production of pro-inflammatory cytokines and may contribute to the pathogenesis of neutrophilic asthma.

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Section: Discussionsupporting

confidence: 49%

Innate immune activation in neutrophilic asthma and bronchiectasis

Simpson

Grissell

Douwes

et al. 2007

Thorax

291

288

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“…Reduced bacterial agglutination, phagocytosis, and intracellular killing all likely contribute to the defect in pulmonary clearance in SP-A -/-mice in this study and others (6,7). However, compared with specific antibody and complement, collectins are actually quite weak opsonins, usually producing only modest enhancement of phagocytosis (up to 2-to 2.5-fold) (3,47).…”

Section: Figure 12supporting

confidence: 46%

Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability

Wu¹,

Kuzmenko²,

Wan³

et al. 2003

J. Clin. Invest.

130

154

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The pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D), have been reported to bind lipopolysaccharide (LPS), opsonize microorganisms, and enhance the clearance of lung pathogens. In this study, we examined the effect of SP-A and SP-D on the growth and viability of Gram-negative bacteria. The pulmonary clearance of Escherichia coli K12 was reduced in SP-A–null mice and was increased in SP-D–overexpressing mice, compared with strain-matched wild-type controls. Purified SP-A and SP-D inhibited bacterial synthetic functions of several, but not all, strains of E. coli, Klebsiella pneumoniae, and Enterobacter aerogenes. In general, rough E. coli strains were more susceptible than smooth strains, and collectin-mediated growth inhibition was partially blocked by coincubation with rough LPS vesicles. Although both SP-A and SP-D agglutinated E. coli K12 in a calcium-dependent manner, microbial growth inhibition was independent of bacterial aggregation. At least part of the antimicrobial activity of SP-A and SP-D was localized to their C-terminal domains using truncated recombinant proteins. Incubation of E. coli K12 with SP-A or SP-D increased bacterial permeability. Deletion of the E. coli OmpA gene from a collectin-resistant smooth E. coli strain enhanced SP-A and SP-D–mediated growth inhibition. These data indicate that SP-A and SP-D are antimicrobial proteins that directly inhibit the proliferation of Gram-negative bacteria in a macrophage- and aggregation-independent manner by increasing the permeability of the microbial cell membrane

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“…SP-A and SP-D can bind, aggregate and opsonize many microorganisms including Gram-negative and Gram-positive bacteria, enveloped viruses like Influenza A Virus (IAV), RSV, non-enveloped viruses like Rotavirus and fungal organisms in order to protect lung from possible infection . In animal studies, the deficiency of SP-A, SP-D or both were associated with increased susceptibility to pulmonary Pseudomonas aeruginosa (LeVine et al, 1998) and Streptococcal infections (LeVine et al, 1997). Also, elevated levels of SP-A and SP-D mRNA in the lungs of neonatal lambs are associated with clearance of Parainfluenza virus-3 (PIV-3) .…”

Section: Discussionmentioning

confidence: 99%

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

Lazic¹,

Wyatt²,

Matić³

et al. 2007

Alcohol

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In addition to neurodevelopmental effects, alcohol consumption at high levels during pregnancy is associated with immunomodulation and premature birth. Premature birth, in turn, is associated with increased susceptibility to various infectious agents such as Respiratory Syncytial Virus (RSV). The initial line of pulmonary innate defense includes the mucociliary apparatus, which expels microorganisms trapped within the airway secretions. Surfactant proteins A and D (SP-A and SP-D, respectively) are additional components of pulmonary innate immunity and have an important role in pulmonary defense against inhaled pathogens. The purpose of this study was to determine if chronic alcohol consumption during the third trimester of pregnancy alters the function of the mucociliary apparatus and expression of SP-A and SP-D of fetal lung epithelia. Sixteen, date-mated ewes were assigned to two different groups; an ethanol exposed group in which ewes received ethanol through surgically implanted intra-abomasal cannula during the third trimester of pregnancy, and a control group in which ewes received the equivalent amount of water instead of ethanol. Within these two groups, ewes were further randomly assigned to a full-term group in which the lambs were naturally delivered, and a pre-term group in which the lambs were delivered prematurely via an abdominal incision and uterotomy. Ethanol was administered 5 times a week as a 40% solution at 1gr/kg of body weight. The mean maternal serum alcohol concentration (SAC) measured 6 hr post administration was 16.3 +/− 4.36 mg/dL. Tracheas from 6 full-term lambs were collected to assess ciliary beat frequency (CBF). The lung tissue from all (24) lambs was collected for immunohistochemistry (IHC) analysis of SP-A and SP-D protein production and fluorogenic realtime quantitative polymerase chain reaction analysis (qPCR) of SP-A and SP-D mRNA levels. Exposure to ethanol during pregnancy significantly blocked stimulated increase in CBF though ethanol-mediated desensitization of cAMP-dependant protein kinase (PKA). In addition, pre-term born/ethanol-exposed lambs showed significantly decreased SP-A m-RNA expression when compared to the pre-term born/control group (p=0.004); no significant changes were seen with SP-D. The full-term/ethanol exposed lambs had no significant alterations in mRNA levels, but had significantly less detectable SP-A protein when compared to the full-term/control lambs (p=0.02).Corresponding author: Tatjana Lazic, DVM, MS, 2740 Veterinary Medicine, Department of Veterinary Pathology, Iowa State University, Ames, Iowa 50011-1250, 515-294-6688, FAX 515-294-5423, tlazic@iastate.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process error...

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Surfactant Protein-a but Not Sp-D Deficient Mice Are Susceptible to Bacterial Infection in the Lung

Cited by 47 publications

References 0 publications

Innate immune activation in neutrophilic asthma and bronchiectasis

Innate immune activation in neutrophilic asthma and bronchiectasis

Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

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