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)

Sputum samples from seven patients with cystic fibrosis and chronic P. aeruginosa lung infection were investigated for immune complexes by PEG precipitation and in two different complement binding assays. All seven patients were immune complex positive. The components involved in immune complex formation were identified by SDS-PAGE and immunoblotting. We found P. aeruginosa lipopolysaccharide as a major antigen. Both core and O-specific saccharide antigens could be demonstrated. IgG and IgA were the immunoglobulins involved, with IgG2 as the dominating IgG subclass. Lipopolysaccharide has a number of biological activities and its presence in sputum may have consequences for the pathogenesis of lung disease in cystic fibrosis.
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PMID:Lipopolysaccharide is present in immune complexes isolated from sputum in patients with cystic fibrosis and chronic Pseudomonas aeruginosa lung infection. 155 93

Tumor necrosis factor-alpha (TNF) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis, in many organ systems, including the lung. It has been suggested that cells from patients infected by the human immunodeficiency virus (HIV + ve) are primed for TNF release. We postulated that TNF release from the alveolar macrophages (AM) of such patients with lung disease might lead to their observed pulmonary dysfunction. We present data confirming that peripheral blood monocytes (PBM) and demonstrating that AM from HIV + ve patients with pulmonary manifestations show significantly greater TNF production than those from HIV-negative (HIV - ve) subjects. In addition, we found sequentially significant increases in TNF production from AM and PBM of HIV + ve patients with no pathogens detected at bronchoscopy (NB), bacterial pneumonia (BP), and those with Pneumocystis carinii pneumonia (PCP). The overall TNF levels were greater from AM than PBM in all groups other than spontaneous production from HIV - ve subjects. Adherent populations of PBM and AM were incubated for 4 h with lipopolysaccharide (10 micrograms/ml) or control medium alone. Cell-free supernatants were examined for the presence of TNF using an immunoassay. The TNF levels (mean +/- SD) in IU/ml from stimulated PBM of the PCP, BP, NB, and control groups, respectively, were 186 +/- 36, 140 +/- 30, 95 +/- 18, and 55 +/- 10 and the spontaneous levels were 123 +/- 25, 100 +/- 22, 75 +/- 24, and 11 +/- 5.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Production of tumor necrosis factor-alpha by blood and lung mononuclear phagocytes from patients with human immunodeficiency virus-related lung disease. 189 44

Leukocytes were obtained from bronchoalveolar lavages (BAL) of 36 patients including 10 with lung cancer, 15 with inflammatory lung diseases and 11 healthy control patients undergoing diagnostic investigation. The entire alveolar cell population responded weakly to the classic interferon (IFN) inducers: Newcastle disease virus (NDV), phytohemagglutinin (PHA) and lipopolysaccharide (LPS). This refers mainly to normal healthy volunteers. Alveolar leukocytes from patients with inflammatory lung diseases and nonsteroid treated lung cancer responded better to the interferon inducers than did cells from other patients. The IFN-alpha or IFN-gamma response of whole blood leukocytes to the same inducers was 10 to 100-fold higher than that of the alveolar cells. Alveolar macrophages from 6 healthy individuals and 3 patients with inflammatory lung disease were cultured in vitro for 6 days. The IFN response to inducers appears to depend on the origin of the cultured cells. It increased in the initially hyporeactive macrophages from healthy subjects and decreased in the relatively reactive cells from the patients with inflammatory lung diseases. We suggest that the hyporeactivity to IFN induction is a physiological state of the alveolar leukocytes which are a specialized cell population having constant exposure to inhaled agents such as dust, smoke, microorganisms and their by-products. The hyporesponsiveness to IFN induction of the alveolar cells may have an important physiological role in protecting lungs against hyperproduction of cytokines involved in the inflammatory and allergic reactions.
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PMID:Hyporesponsiveness of human alveolar leukocytes to interferon-alpha and interferon-gamma inducers. 212 76

Antibody opsonins from cystic fibrosis (CF) patients were investigated using nonmucoid and mucoid lipopolysaccharide (LPS) immunotype 1 Pseudomonas aeruginosa as bacterial ligands and PMN phagocytes. CF sera were compared to normal sera, polyvalent PA LPS hyperimmune globulin, and isotype switch variant monoclonal antibodies (MAbs) specific for type 1 PA LPS. Sera from PA-infected CF patients (CF PA+) had elevated levels of PA LPS and alginate IgG antibodies and promoted significantly greater antibody-dependent PMN chemiluminescence responses than sera from uninfected CF patients (CF PA-) or normal human sera (NHS). After adjustment for autologous IgG PA LPS antibody content, however, CF PA+ sera had less antibody-dependent opsonic activity than sera from CF PA- patients (P less than 0.025) or NHS (P less than 0.0025), suggesting qualitative opsonic defects of IgG PA LPS antibodies in CF PA+ sera. Antigen-specific immunoprecipitation of PA LPS antibodies enhanced opsonization by 40% of CF PA+ sera while uniformly reducing that from CF PA- sera (P less than 0.01), indicating LPS-specific nonopsonic antibodies in some CF PA+ sera. Alginate antibodies were not critical opsonins in most uninfected CF patient sera. PA LPS IgG antibodies isolated by immunoaffinity chromatography from NHS, hyperimmune globulin, and CF PA- sources were opsonic and had greater activity at equal antigen-binding concentration than identical antibodies isolated from infected CF patients (P less than 0.01-0.05); the majority of isolates from CF PA+ sera did not promote PMN oxidative responses above nonopsonic baseline. A potential isotypic basis for these findings was supported by differences in PMN responses to PA opsonized with MAbs of identical specificity but differing isotypes. PA LPS-specific IgG antibodies inhibiting PMN oxidative responses in infected patient sera demonstrate antigen-specific immunomodulation of host responses by chronic bacterial parasitism in CF, which may play a role in the pathophysiology of lung disease.
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PMID:Nonopsonic antibodies in cystic fibrosis. Pseudomonas aeruginosa lipopolysaccharide-specific immunoglobulin G antibodies from infected patient sera inhibit neutrophil oxidative responses. 251 30

Interleukin-1 (IL-1) release by alveolar macrophages (AMs) from 29 patients with primary bronchogenic carcinoma, lung metastases, acute pneumonitis, and chronic infection was evaluated in response to a standard stimulus, lipopolysaccharide (LPS). The results were compared to those of AMs from normal smokers or nonsmokers (volunteers). AMs derived from healthy smokers secreted significantly more IL-1 than AMs from nonsmokers. In contrast, AMs from smokers affected with primary lung cancer have lost their capacity of secreting high levels of IL-1, whereas IL-1 secretion was high in nonsmokers with hematogenous metastases. AMs release high IL-1 levels in patients with acute bacterial infections. A significant correlation exists between numbers of AMs and IL-1 levels in normal individuals, a relationship which disappears in patients. These observations suggest that AMs in inflammatory lung disease, even discrete, have an increased capacity to secrete IL-1 on stimulation with LPS. They also suggest that an intrinsic dysfunction of AMs may accompany primary bronchogenic carcinoma. The influence of tobacco in modifying the functions of AMs is stressed.
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PMID:Interleukin-1 secretion by lipopolysaccharide-stimulated alveolar macrophages. Relationships to cell numbers--influence of smoking habits. 281 73

The relevance of circulating immune complexes, plasma complement activation, and serum antibodies against discrete antigens of Pseudomonas aeruginosa, to the clinical course in patients with cystic fibrosis (CF) is unknown. We related these factors to outcome in 49 patients with CF colonized by P. aeruginosa, comparing 14 who died of lung disease with 35 survivors of similar age and duration of colonization, as well as 9 uncolonized patients with CF, 24 patients with other bronchorrheic lung disease, and 10 healthy control subjects. The patients with CF colonized by P. aeruginosa who died had a higher incidence of immune complexes than did survivors (71 versus 40%, p less than 0.05). Moreover, C4 activation was highly associated with immune complexes and mortality (p less than 0.001 for each). Those who died also had much higher levels of IgG antibodies to P. aeruginosa lipopolysaccharide (LPS) and exotoxin A than did survivors colonized by P. aeruginosa (p less than 0.005 and p = 0.01, respectively), whereas both groups had similar levels of P. aeruginosa sonicate, elastase, alkaline protease, and endotoxin core antibodies. We conclude that increasing levels of serum IgG antibodies to P. aeruginosa LPS and exotoxin A and the presence of systemic immune complexes and complement activation are associated with poor prognosis in CF, and may provide useful noninvasive markers for studying the possible immunopathogenesis of CF lung disease.
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PMID:Association of systemic immune complexes, complement activation, and antibodies to Pseudomonas aeruginosa lipopolysaccharide and exotoxin A with mortality in cystic fibrosis. 308 45

The systemic humoral immune response in cystic fibrosis (CF) to outer membrane (OM) proteins of Pseudomonas aeruginosa was investigated as a function of the time of colonization by immunoblotting. OM proteins were prepared from bacteria grown in ion-sufficient, magnesium-depleted, and iron-deficient media. The location of proteins F, H, and I on the blots was verified by monoclonal antibodies. Proteins H2 and H1 were differentiated by the overexpression of H1 under magnesium depletion. Iron-regulated membrane proteins (IRMPs) were recognized by their overproduction under iron limitation. Plasma samples from 43 CF patients and ten healthy adults were analyzed after preadsorption with lipopolysaccharide (LPS). Within the first year of colonization, only two to six specific plasma antibodies to OM proteins were produced. After a strong increase during the second year, long-lasting levels were seen in the majority of patients. Large variations of the immune response were noted among the patients. The number of specific antibodies to different OM proteins correlated with the severity of the course of lung disease. At maximum 38 immunostained bands were observed. Proteins H and I were the earliest antigens amongst the major OM proteins. During the second year, antibodies directed to protein F became detectable. IRMPs which indicate the growth of P. aeruginosa under iron deprivation were only recognized by plasma samples from chronically colonized CF patients with advanced lung disease.
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PMID:Immune response in cystic fibrosis to outer membrane proteins of Pseudomonas aeruginosa. 314 71

Interleukin 1 secretion from human alveolar macrophages was studied in patients with interstitial pulmonary fibrosis, sarcoidosis, and the acquired immunodeficiency syndrome with pneumonitis and compared to secretion from alveolar macrophages of normal volunteers. Macrophages lavaged from the lungs were stimulated with 10 micrograms/ml of lipopolysaccharide and cultured for 24 hr. In some cases macrophages were also stimulated with 1 microgram/ml lipopolysaccharide. After dialysis of the culture supernatants, interleukin 1 secretion was quantified by the thymocyte proliferation assay and probit analysis and expressed in terms of secretion from 1 million macrophages. Results showed that, on average, macrophages derived from patients secreted more interleukin 1 after stimulation with lipopolysaccharide compared to normal subjects. Mean secretion was significantly greater from macrophages of patients with acquired immunodeficiency syndrome and interstitial pulmonary fibrosis when stimulated with 10 micrograms/ml lipopolysaccharide. Of the 24 individuals studied, spontaneous interleukin 1 secretion was detected from unstimulated macrophages in only 1 patient and 1 normal volunteer. We conclude that alveolar macrophages lavaged from the lungs of patients with inflammatory lung disease have an increased capacity to secrete interleukin 1 on in vitro stimulation with lipopolysaccharide. Possible mechanisms for this increase are discussed.
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PMID:Interleukin 1 secretion from human alveolar macrophages in lung disease. 348 3

Human alveolar macrophages obtained from 7 normal volunteers and 7 patients with lung disease were stimulated with endotoxin (lipolysaccharide) to induce interleukin 1/leucocytic pyrogen (IL1/LP) secretion. Using the thymocyte assay we quantitated IL1/LP activity in macrophage supernatants obtained after 24 h. 10 micrograms/ml lipopolysaccharide stimulated alveolar macrophages to secrete significantly more IL1/LP activity than did 1 micrograms/ml. Apart from one patient with sarcoidosis, the presence of indomethacin did not significantly inhibit the quantity of IL1/LP secreted in response to LPS. We also demonstrated that the presence of indomethacin did not affect the response of thymocytes to IL1/LP. We conclude that the secretion of IL1/LP by human alveolar macrophages in response to endotoxin is not significantly reduced by the cyclooxygenase inhibitor indomethacin.
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PMID:Secretion of interleukin 1/leucocytic pyrogen from endotoxin-stimulated human alveolar macrophages is unaffected by indomethacin. 349 Apr 58

The production of PAF was studied in alveolar macrophages (AM) and neutrophils recovered by bronchial lavage from guinea pigs exposed to aerosolized bacterial endotoxin (lipopolysaccharide, LPS). The amount of cell-associated PAF was estimated by measuring serotonin release from rabbit platelets. An increased and dose-related production was found in AM for as long as 2 h after a 40-min exposure. No production was detectable after 4 h. Prolonging the exposure did not prolong the response. When a second exposure was given, no PAF could be detected until the time interval between the 2 exposures was 72 h. The amount of neutrophils in lung lavage fluid was elevated about 100 times at 4 h after the exposure, but only a minor PAF production was found in these cells. In view of the role of LPS-contaminated dusts for the development of human lung disease, particularly airway constriction, the role of PAF needs to be further investigated.
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PMID:Inhalation of endotoxin stimulates alveolar macrophage production of platelet-activating factor. 354 18


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