Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine macrophages of the P388D1 cell line stimulated with lipopolysaccharide (LPS) from Haemophilus actinomycetemcomitans Y4 released an interleukin-1 (IL-1) inhibitor, as well as IL-1. Maximal IL-1 activity in culture supernatants was detected after 24 h of culture. On the other hand, IL-1 inhibitor activity reached a maximum level after 72 h of culture. An IL-1 inhibitor was partially purified from the culture supernatant of P388D1 cells stimulated with Y4 LPS for 72 h by ammonium sulfate precipitation, followed by Sephacryl S-200 gel chromatography. A 160-kilodalton peak inhibitory to IL-1 and a 14-kilodalton peak showing IL-1 activity were separated by Sephacryl S-200 column chromatography. The partially purified IL-1 inhibitor significantly suppressed the proliferation of C3H/HeJ murine thymocytes that had been induced with murine and human IL-1 in the presence of a submitogenic dose of concanavalin A. The IL-1 inhibitor more strongly suppressed human recombinant IL-1 beta than human recombinant IL-1 alpha. This inhibitory activity of the partially purified preparation was unaffected by the presence of trypsin inhibitor and the protease inhibitor aprotinin. The IL-1 inhibitor did not exhibit either IL-2 or IL-2 inhibitor activity. The inhibitor suppressed C3H/HeJ thymocyte proliferation induced by IL-1 in the presence of a saturated concentration of IL-2 instead of a suboptimal concentration of concanavalin A. These results indicate that prolonged culture of Y4 LPS-stimulated murine macrophages releases a specific inhibitor of IL-1.
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PMID:Production of an interleukin-1 inhibitor by cell line P388D1 murine macrophages stimulated with Haemophilus actinomycetemcomitans lipopolysaccharide. 326 86

To determine the extent of airway infection and inflammation in adolescents and adults with cystic fibrosis (CF) who have mild lung disease and are without symptoms of active infection, we performed bronchoalveolar lavage (BAL) on 18 CF patients > or = 12 yr of age who were stable, appeared clinically well, and had mean (+/- SEM) FEV1 of 79 +/- 4% of predicted. We quantitated the bacteria, inflammatory cells, immunoglobulins, and mediators of inflammatory tissue damage in the epithelial lining fluid (ELF) of these patients and in 23 healthy control subjects. All CF patients were found to be infected with Pseudomonas aeruginosa, Staphylococcus aureus, and/or Haemophilus influenzae; no organisms were isolated from the control subjects. The mean number of cells in the ELF was 14 times greater in the CF patients than in the control subjects. Neutrophils constituted 57% of the recovered cells in the CF patients versus 3% in the control subjects, and their concentration was 380 times greater in the CF patients versus the control subjects. IgG, IgA, and IgM were 2.5 to 6 times greater in CF ELF versus that of control subjects. Abundant active elastase was present in the ELF of the CF patients (2.3 +/- 0.9 microM) despite threefold elevated levels of alpha 1-protease inhibitor (alpha 1-PI). No active elastase was detectable in the control subjects. alpha 1-PI was functional in CF as demonstrated by elevated elastase:alpha 1-PI complex (0.045 microM in CF versus 0.002 microM in control subjects). This active elastase caused proteolytic destruction of surface complement receptors on airway neutrophils in situ.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. 804 28

The acute phase reactant and protease inhibitor alpha(1)-antichymotrypsin is considered to play a protective role in the airways, but whether it interacts with respiratory bacteria is not known. We analyzed whether the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and other bacterial species interact with antichymotrypsin. M. catarrhalis was the only species that bound antichymotrypsin among 25 bacterial species tested by flow cytometry and direct binding assay. We compared a series of clinical isolates in addition to wild-type and ubiquitous surface protein-deficient Moraxella to study the nature of antichymotrypsin binding by the bacteria. Experiments with Moraxella mutants revealed that ubiquitous surface proteins A1 and A2 were responsible for the interaction, and using recombinant fragments, a consensus sequence within ubiquitous surface proteins A1 and A2 was defined. Binding of iodine-labeled antichymotrypsin was dose dependent and strong (dissociation constant [K(d)] 24.9-44.8 nM). Moreover, a chymotrypsin activity assay showed that antichymotrypsin, when bound to the bacterial surface, was neutralized. Moraxella antichymotrypsin neutralization is a novel microbial virulence mechanism that may induce excessive inflammation resulting in more exposed extracellular matrix that is beneficial for bacterial colonization.
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PMID:Moraxella-dependent alpha 1-antichymotrypsin neutralization: a unique virulence mechanism. 1809 71