Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relationships between lung function and surfactant function and composition were examined during the evolution of acute lung injury in guinea pigs. Lung mechanics and gas exchange were assessed 12, 24, or 48 h after exposure to nebulized lipopolysaccharide (LPS). Bronchoalveolar lavage (BAL) fluid was processed for phospholipid and protein contents and surfactant protein (SP) A and SP-B levels; surfactant function was measured by pulsating bubble surfactometry. Lung elastance, tissue resistance, and arterial-alveolar gradient were moderately elevated by 12 h after LPS exposure and continued to increase over the first 24 h but began to recover between 24 and 48 h. Similarly, the absolute amount of 30,000 g pelleted SP-A and SP-B, the phospholipid content of BAL fluid, and surfactant function declined over the first 24 h after exposure, with recovery between 24 and 48 h. BAL fluid total protein content increased steadily over the first 48 h after LPS nebulization. In this model of acute lung injury, the intra-alveolar repletion of surfactant components in early recovery led to improved surfactant function despite the presence of potentially inhibitory plasma proteins.
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PMID:Determinants of surfactant function in acute lung injury and early recovery. 1092 58

Although several studies have demonstrated that the pulmonary collectins surfactant protein (SP)-A and SP-D contribute to innate immunity by enhancing pathogen phagocytosis, the role of SP-A and SP-D in regulating production of free radicals and cytokines is controversial. We hypothesized that the state and mechanism of activation of the immune cell influence its response to SP-A. The effects of SP-A and SP-D on production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were assessed in isolated rat alveolar macrophages activated with lipopolysaccharide (LPS), interferon gamma (IFN-gamma), or both agonists. SP-A inhibited production of NO and iNOS in macrophages stimulated with smooth LPS, which did not significantly bind SP-A, or rough LPS, which avidly bound SP-A. In contrast, SP-A enhanced production of NO and iNOS in cells stimulated with IFN-gamma or INF-gamma plus LPS. Neither SP-A nor SP-D affected baseline NO production, and SP-D did not significantly affect production of NO in cells stimulated with either LPS or IFN-gamma. These results suggest that SP-A contributes to the lung inflammatory response by exerting differential effects on the responses of immune cells, depending on their state and mechanism of activation.
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PMID:Surfactant protein A differentially regulates IFN-gamma- and LPS-induced nitrite production by rat alveolar macrophages. 1110 30

This study examines the relationships between inflammation, surfactant protein (SP) expression, surfactant function, and lung physiology in a murine model of acute lung injury (ALI). 129/J mice received aerosolized endotoxin lipopolysaccharide [LPS] daily for up to 96 h to simulate the cytokine release and acute inflammation of ALI. Lung elastance (E(L)) and resistance, lavage fluid cell counts, cytokine levels, phospholipid and protein content, and surfactant function were measured. Lavage and lung tissue SP content were determined by Western blot and immunohistochemistry, and tissue messenger RNA (mRNA) levels were assessed by Northern blot and in situ hybridization. Tumor necrosis factor-alpha and neutrophil counts in bronchoalveolar lavage fluid increased within 2 h of LPS exposure, followed by increases in total protein, interleukin (IL)-1beta, IL-6, and interferon-gamma. E(L) increased within 24 h of LPS exposure and remained abnormal up to 96 h. SP-B protein and mRNA levels were decreased at 24, 48, and 96 h. By contrast, SP-A protein and mRNA levels and SP-C mRNA levels were not reduced. Surfactant dysfunction occurred coincident with changes in SP-B levels. This study demonstrates that lung dysfunction in mice with LPS-ALI corresponds closely with abnormal surfactant function and reduced SP-B expression.
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PMID:Decreased surfactant protein-B expression and surfactant dysfunction in a murine model of acute lung injury. 1147 73

Infection of the respiratory tract is a frequent cause of lung pathologies, morbidity, and death. When bacterial endotoxin [lipopolysaccharide (LPS)] reaches the alveolar spaces, it encounters the lipid-rich surfactant that covers the epithelium. Although binding of hydrophilic surfactant protein (SP) A and SP-D with LPS has been established, nothing has been reported to date on possible cross talks between LPS and hydrophobic SP-B and SP-C. We designed a new binding technique based on the incorporation of surfactant components to lipid vesicles and the separation of unbound from vesicle-bound LPS on a density gradient. We found that among the different hydrophobic components of mouse surfactant separated by gel filtration or reverse-phase HPLC, only SP-C exhibited the capacity to bind to a tritium-labeled LPS. The binding of LPS to vesicles containing SP-C was saturable, temperature dependent, related to the concentrations of SP-C and LPS, and inhibitable by distinct unlabeled LPSs. Unlike SP-A and SP-D, the binding of SP-C to LPS did not require calcium ions. This LPS binding capacity of SP-C may represent another antibacterial defense mechanism of the lung.
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PMID:Interaction of bacterial lipopolysaccharide with mouse surfactant protein C inserted into lipid vesicles. 1155 81

Intra-amniotic lipopolysaccharide (LPS) and cytokines may decrease respiratory distress syndrome (RDS) and increase chronic lung disease in the newborn. The aim was to identify the primary inflammatory mediators regulating the expression of surfactant proteins (SP) in explants from immature (22-day-old fetus) and mature (30-day term fetus and 2-day-old newborn) rabbits. In immature lung, interleukin (IL)-1alpha and IL-1beta upregulated the expression of SP-A and SP-B. These effects of IL-1 were diminished, and SP-C mRNA was suppressed additively in the presence of tumor necrosis factor (TNF)-alpha and either LPS or interferon (IFN)-gamma. LPS, TNF-alpha, or IFN-gamma had no effect alone. In explants from the term fetus and the newborn, LPS, IL-1alpha, and TNF-alpha additively suppressed the SPs. LPS acutely induced IL-1alpha in alveolar macrophages in mature lung but not in the immature lung. IFN-gamma that generally has low expression in intrauterine infection decreased the age dependence of the other agonists' effects on SPs. The present study serves to explain the variation of the pulmonary outcome after an inflammatory insult. We propose that IL-1 from extrapulmonary sources induces the SPs in premature lung and is responsible for the decreased risk of RDS in intra-amniotic infection.
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PMID:Regulation of surfactant proteins by LPS and proinflammatory cytokines in fetal and newborn lung. 1188 Mar 7

Pulmonary surfactant protein (SP)-A, an innate immune molecule, modifies lipopolysaccharide (LPS)-induced cell responses. Because SP-A avidly binds to the deep rough (Re) mutant of LPS, we first investigated the functional consequences of this interaction and found that preincubation of Re-LPS with SP-A significantly and in a dose-dependent manner decreased the sensitivity of rat alveolar macrophages and human mononuclear cells to Re-LPS-induced activation at limited amounts of LPS-binding protein (LBP). At high LBP concentrations, the SP-A-mediated cellular inhibition of Re-LPS-induced activation was abrogated. Because LBP-catalyzed binding of LPS to CD14 is essential for low-dose LPS-induced signaling, we then hypothesized that SP-A inhibits Re-LPS-induced immune cell activation via inhibiting the binding of Re-LPS to LBP. Binding competition experiments employing a surface plasmon resonance technique showed that Re-LPS preincubated with SP-A bound to LBP to a significantly lesser extent than Re-LPS alone. For enhanced cellular association of [(3)H]LPS/SP-A complexes to occur, the expression of membrane-bound CD14 by human embryonic kidney cells 293 was not essential. Therefore, the ability of SP-A to inhibit immune cell activation by Re-LPS may be due to its ability to block the binding of Re-LPS to LBP and prevent the initiation of the LBP/CD14 pathway for inflammatory reactions in the lung.
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PMID:Surfactant protein a inhibits lipopolysaccharide-induced immune cell activation by preventing the interaction of lipopolysaccharide with lipopolysaccharide-binding protein. 1220 98

We investigated the role of the surfactant proteins (SPs) A and D in the pulmonary immune defense of nonmucoid strains of Pseudomonas aeruginosa, the most etiologic agents of nosocomial Pseudomonas pneumonia. We first examined the interactions of recombinant human SP-D dodecamers and purified natural or recombinant human SP-A with two smooth, and two rough, clinical isolates of nonmucoid P. aeruginosa. SP-D bound to all four isolates, but agglutinated only one rough and one smooth strain. SP-D functioned as an opsonin to enhance the uptake of all four strains by the human monocytic cell line Mono Mac 6 (MM6). SP-D also enhanced tumor necrosis factor-alpha secretion by MM6 cells in response to purified lipopolysaccharide (LPS) isolated from the rough, but not the smooth, strains. Although SP-A bound to all four strains, it did not cause bacterial aggregation or enhance uptake. It showed small but statistically significant inhibitory effects on the cytokine response of MM6 cells to one strain of smooth organisms, but did not significantly alter the response to purified LPS. This study in combination with previously published data strongly suggests that SP-D may play important roles in the local innate pulmonary defense against nonmucoid P. aeruginosa of diverse LPS phenotypes, and preferentially augments the cellular response to rough P. aeruginosa endotoxin.
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PMID:Surfactant protein A and D differently regulate the immune response to nonmucoid Pseudomonas aeruginosa and its lipopolysaccharide. 1254 Apr 93

Pulmonary surfactant and its components are part of the first-line immune defense within the lung. Here the authors show that the surfactant protein (SP) SP-D, but not SP-A, agglutinates some clinical isolates of Pseudomonas aeruginosa and Stenotrophomonas maltophilia. No agglutination of Staphylococcus aureus or Burkholderia cepacia was observed. The SP-D-induced agglutination of P. aeruginosa was not dependent on a specific lipopolysaccharide (LPS) serotype. The authors also show that SP-D, but not SP-A, increased the tumor necrosis factor (TNF alpha) release from human monocytic cells in response to a subset of P. aeruginosa and P. aeruginosa LPS. A clinical preparation of surfactant (Alveofact) blocked the TNF alpha release from monocytic cells induced by P. aeruginosa or its LPS. SP-A reversed the inhibitory effect of Alveofact in 6/8 strains of P. aeruginosa and 2/9 preparations of P. aeruginosa LPS. SP-D did not significantly alter the TNF alpha production induced by vital P. aeruginosa in the presence of Alveofact but markedly increased the TNF alpha release induced by a preparation of rough and smooth P. aeruginosa LPS. In summary, this study shows that the immunomodulatory properties of SP-A and SP-D specifically depend on the colonizing strain of P. aeruginosa. In addition, the authors show that the function of SP-A and SP-D is modulated in the presence of surfactant lipids.
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PMID:Cytokine stimulation by Pseudomonas aeruginosa--strain variation and modulation by pulmonary surfactant. 1519 51

Administration of lipopolysaccharide (LPS) to experimental animals results in the up-regulation of expression of the plasma form of platelet-activating factor acetylhydrolase (PAF AH) in tissue macrophages. To investigate the mechanism underlying induction of PAF AH by LPS we used murine RAW264.7 and human THP-1 macrophages as model systems. We found that the p38 mitogen-activated protein kinase (p38 MAPK) pathway mediates transcriptional activation of the PAF AH gene through the participation of nucleotides -68/-316 relative to the transcriptional initiation site. This promoter region spans two Sp1/Sp3 binding sites (SP-A and SP-B) and is necessary and sufficient for the observed effect. Disruption of these Sp binding sites significantly reduces promoter activity in LPS-stimulated cells. The ability of LPS to induce transcriptional activation of PAF AH is not due to enhanced Sp1/Sp3 binding to the promoter but involves enhanced transactivation function of Sp1 via p38 MAPK activation. These studies characterize the mechanism by which LPS modulates expression of PAF AH at the transcriptional level, and they have important implications for our understanding of responses that occur during the development of LPS-mediated inflammatory diseases.
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PMID:The p38 MAPK pathway mediates transcriptional activation of the plasma platelet-activating factor acetylhydrolase gene in macrophages stimulated with lipopolysaccharide. 1521 49

The collectin surfactant protein (SP)-A has been implicated in multiple immunoregulatory functions of innate pulmonary host defense via modulating immune responses both in vitro and in vivo. The aim of the present study was to investigate mechanisms responsible for the anti-inflammatory effects of human (hu) SP-A on the inhibitory kappaB (IkappaB)/nuclear factor (NF)-kappaB signaling pathway in alveolar macrophages (AMs). Initial CD25 expression analysis by flow cytometry of CD14/hu Toll-like receptor 4-transfected Chinese hamster ovary reporter cells demonstrated that SP-A alone does not induce any NF-kappaB-dependent CD25 expression in these cells. In AMs, SP-A pretreatment caused a marked inhibition of lipopolysaccharide (LPS)-induced NF-kappaB activation independent of the LPS chemotype used as determined by electrophoretic mobility shift assay. Western blot analysis revealed that SP-A by itself increased the protein expression of IkappaB-alpha, the predominant regulator for rapidly induced NF-kappaB, in a dose- and time-dependent manner without enhancing IkappaB-alpha messenger RNA as determined by reverse transcription-polymerase chain reaction. SP-A did not interfere with LPS-induced serine(32) phosphorylation of IkappaB-alpha but significantly enhanced IkappaB-alpha abundance under LPS-coupled conditions. The data suggest that anti-inflammatory effects of SP-A on LPS-challenged AMs are associated with a SP-A-mediated direct modulation of the IkappaB-alpha turnover in these cells.
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PMID:Accumulation of inhibitory kappaB-alpha as a mechanism contributing to the anti-inflammatory effects of surfactant protein-A. 1530 5


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