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)

The extracellular antigens of Actinobacillus actinomycetemcomitans Y4 (serotype b) contain a 37-kDa protein which is a major target for IgGs from patients suffering from severe alveolar bone loss. Since the 37-kDa protein has not been studied sufficiently, our investigation focused on its characteristics, e.g., its localization, specificity, and whether it directly stimulates macrophages to produce cytokines. The 37-kDa protein was purified from the culture supernatant of the Y4 strain by means of chromatofocusing and gel filtration. The 37-kDa protein is a unique glycoprotein which forms immune complexes with monoclonal antibodies against rhamnose-fucose polysaccharide. Patients with A. actinomycetemcomitans-associated periodontitis had higher antibody titers to the purified 37-kDa protein than healthy subjects (p < 0.001). Anti-37-kDa protein antibodies recognized a 37-kDa band in the cytosolic, ribosomal, and total membrane fractions from Y4 cells. Extracellular substances from other strains of A. actinomycetemcomitans (serotypes a and c) also reacted in the Western blots, but Haemophilus spp. or several periodontopathic bacteria did not. These results suggested that the 37-kDa protein is a cytosolic protein that is passed through the cell membrane, and its protein portion is specific for A. actinomycetemcomitans but common to serotypes. This protein induced Il-1 beta, Il-6, and TNF-alpha release from murine macrophages. The Il-6-inducing activity of the 37-kDa protein was higher than that of LPS. These findings suggested that the 37-kDa protein which is released from live cells plays a role in A. actinomycetemcomitans-associated periodontitis, as antigen inducing the release of inflammatory cytokines which are associated with alveolar bone loss.
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PMID:Extracellular 37-kDa antigenic protein from Actinobacillus actinomycetemcomitans induces TNF-alpha, IL-1 beta, and IL-6 in murine macrophages. 929 87

The adjuvanticity of the phosphazene polymer, poly[di(carboxylatophenoxy) phosphazene] (PCPP) was examined with a diverse collection of immunogens. PCPP proved to be a potent adjuvant for trivalent influenza virus vaccine, tetanus toxoid, hepatitis B surface antigen, herpes simplex virus glycoprotein gD2 and the capsular polysaccharide, polyribosylribitolphosphate, from Haemophilus influenzae type b. Taken together these results clearly demonstrate the general utility of PCPP as an adjuvant. Furthermore, PCPP was a superior adjuvant at least with TT compared to similar negatively charged polyanions, polymethylacrylic acid and polyacrylic acid.
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PMID:PCPP as a parenteral adjuvant for diverse antigens. 955 61

The relationships between 4 bacterial and 3 viral antibody titers and morbidity (undifferentiated fever (UF)) and mortality were investigated in recently weaned beef calves. Blood samples from 100 animals that required treatment for UF (Cases) and 100 healthy control animals (Controls) were obtained: upon arrival at the feedlot (Arrival), at the time of selection as a Case or Control (Selection), and at approximately 33 d of the feeding period (Convalescent). Seroconversion to Pasteurella haemolytica antileukotoxin was associated with an increased risk of UF (OR = 2.83); however, seroconversion to bovine herpesvirus-1 G-IV glycoprotein was associated with a decreased risk of UF (OR = 0.43). Higher Arrival bovine viral diarrhea virus antibody titer was associated with a decreased risk of UF (OR = 0.83). Increases in Mycoplasma alkalescens antibody titer after Arrival were associated with an increased risk of UF (OR = 1.10). Higher Arrival Haemophilus somnus antibody titer and increases in Haemophilus somnus antibody titer after Arrival were both associated with a decreased risk of UF (OR = 0.76 and OR = 0.78). The odds of overall mortality (OR = 5.09) and hemophilosis mortality (OR = 11.31) in Cases were significantly (P < 0.05) higher than in the Controls. Higher Arrival bovine herpesvirus-1 antibody titer was associated with an increased risk of mortality (OR = 1.30). Protective immunity to Pasteurella haemolytica antileukotoxin, Haemophilus somnus, bovine herpesvirus-1 G-IV glycoprotein, bovine viral diarrhea virus, and Mycoplasma spp. may be necessary to reduce the occurrence of UF. Animals with UF are at an increased risk of overall and hemophilosis mortality.
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PMID:Seroepidemiology of undifferentiated fever in feedlot calves in western Canada. 991 66

Surfactant protein (SP)-D is an oligomeric glycoprotein belonging to the family of collagen-like lectins known as collectins, which have previously been shown to stimulate phagocytosis and other immune cell functions. The hypothesis investigated in this study was that SP-D would stimulate the phagocytosis of an important pulmonary pathogen, Pseudomonas aeruginosa. SP-D, isolated from the lavage fluid of silica-treated rats, significantly enhanced the uptake of three of six strains of P. aeruginosa by rat alveolar macrophages as analyzed by both fluorescence and electron microscopy. SP-D had only minimal effects on phagocytosis of Haemophilus influenzae. SP-D bound to live P. aeruginosa, and binding was inhibited by chelation of calcium and by a competing saccharide, inositol. In vitro killing assays demonstrated that macrophage-mediated killing of one of the mucoid strains of P. aeruginosa was modestly enhanced by SP-D. P. aeruginosa was not measurably aggregated by SP-D either macroscopically or microscopically. Further, SP-D does not appear to act as an activation ligand because adherence of macrophages to SP-D- coated slides did not stimulate the uptake of P. aeruginosa. These findings suggest that SP-D may be important in controlling the pathogenesis of P. aeruginosa in the lung.
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PMID:Surfactant protein D stimulates phagocytosis of Pseudomonas aeruginosa by alveolar macrophages. 1053 13

The antiphospholipid syndrome (APS) is characterized by the presence of pathogenic autoantibodies against beta2-glycoprotein-I (beta2GPI). The factors causing production of anti-beta2GPI remain unidentified, but an association with infectious agents has been reported. Recently, we identified a hexapeptide (TLRVYK) that is recognized specifically by a pathogenic anti-beta2GPI mAb. In the present study we evaluated the APS-related pathogenic potential of microbial pathogens carrying sequences related to this hexapeptide. Mice immunized with a panel of microbial preparations were studied for the development of anti-beta2GPI autoantibodies. IgG specific to the TLRVYK peptide were affinity purified from the immunized mice and passively infused intravenously into naive mice at day 0 of pregnancy. APS parameters were evaluated in the infused mice on day 15 of pregnancy. Following immunization, high titers of antipeptide [TLRVYK] anti-beta2GPI Ab's were observed in mice immunized with Haemophilus influenzae, Neisseria gonorrhoeae, or tetanus toxoid. The specificity of binding to the corresponding target molecules was confirmed by competition and immunoblot assays. Naive mice infused with the affinity-purified antipeptide Ab's had significant thrombocytopenia, prolonged activated partial thromboplastin time and elevated percentage of fetal loss, similar to a control group of mice immunized with a pathogenic anti-beta2GPI mAb. Our study establishes a mechanism of molecular mimicry in experimental APS, demonstrating that bacterial peptides homologous with beta2GPI induce pathogenic anti-beta2GPI Ab's along with APS manifestations.
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PMID:Bacterial induction of autoantibodies to beta2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome. 1190 Nov 88

Many cell types in the airway express the adhesive glycoprotein for leukocytes intercellular adhesion molecule-1 (ICAM-1) constitutively and/or in response to inflammatory stimuli. In this study, we identified functions of ICAM-1 on airway epithelial cells in defense against infection with Haemophilus influenzae. Initial experiments using a mouse model of airway infection in which the bacterial inoculum was mixed with agar beads that localize inflammation in airways demonstrated that ICAM-1 expression was required for efficient clearance of H. influenzae. Airway epithelial cell ICAM-1 expression required few or no leukocytes, suggesting that epithelial cells could be activated directly by interaction with bacteria. Specific inhibition of ICAM-1 function on epithelial cells by orotracheal injection of blocking antibodies resulted in decreased leukocyte recruitment and H. influenzae clearance in the airway. Inhibition of endothelial cell ICAM-1 resulted in a similar decrease in leukocyte recruitment but did not affect bacterial clearance, indicating that epithelial cell ICAM-1 had an additional contribution to airway defense independent of effects on leukocyte migration. To assess this possibility, we used an in vitro model of neutrophil phagocytosis of bacteria and observed significantly greater engulfment of bacteria by neutrophils adherent to epithelial cells expressing ICAM-1 compared with nonadherent neutrophils. Furthermore, bacterial phagocytosis and killing by neutrophils after interaction with epithelial cells were decreased when a blocking antibody inhibited ICAM-1 function. The results indicate that epithelial cell ICAM-1 participates in neutrophil recruitment into the airway, but its most important role in clearance of H. influenzae may be assistance with neutrophil-dependent bacterial killing.
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PMID:Modulation of airway inflammation and bacterial clearance by epithelial cell ICAM-1. 1516 75

One component of the anti-microbial function of lactoferrin (Lf) is its ability to sequester iron from potential pathogens. To overcome this iron limitation, a number of gram-negative bacterial pathogens have developed a mechanism for acquiring iron directly from this host glycoprotein. This mechanism involves surface receptors capable of specifically binding Lf from the host, removing iron and transporting it across the outer membrane. The iron is then bound by a periplasmic iron-binding protein, FbpA, and transported into the cell via an inner membrane complex comprised of FbpB and FbpC. The receptor has been shown to consist of two proteins, LbpA and LbpB. LbpB is bilobed lipoprotein anchored to the outer membrane via fatty acyl groups attached to the N-terminal cysteine. LbpA is a homologue of siderophore receptors, which consist of an N-terminal plug and a C-terminal beta-barrel region. We propose that the receptor proteins, LbpA and LbpB, induce conformational changes in human Lf (hLf) that lower its affinity for iron that binding by FbpA can drive the transport across the outer membrane, a mechanism shared with transferrin (Tf) receptors. The interaction between the receptor proteins and Lf is quite extensive and has been previously studied by using chimeric proteins comprised of Lf & Tf. In an attempt to evaluate the role of FbpA in the transport process, a series of site-directed mutants of FbpA were prepared and used to replace the wild-type protein in the iron acquisition pathway. The mutations were made in the iron-binding and anion-binding ligands of FbpA and were designed to result in altered binding properties. Protein crystallography of the iron-bound form of the Q58L mutant protein revealed that it was in the open conformation with iron coordinated by Y195 and Y196 from the C-terminal domain but not by the other iron-liganding amino acids from the N-terminal domain, H9 and E57. Replacement of the native FbpA in Neisseria meningitidis with wild-type or mutant Haemophilus influenzae FbpAs resulted in a defect in growth on Tf or Lf, suggesting that there may be a barrier to functional expression of H. influenzae FbpAs in Neisseria meningitidis. Thus mutants of the N. meningitidis FbpA are being prepared to replace wild-type protein in order to test their ability to mediate transport from hLf.
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PMID:Lactoferrin receptors in gram-negative bacteria: insights into the iron acquisition process. 1522 71

Like many other autoimmune diseases, the antiphospholipid syndrome (APS) is considered as of a multifactorial etiology, mainly genetic susceptibility coinciding with environmental triggers, of which infectious agents are considered most prominent. Different clinical and experimental studies of the beta2 glycoprotein I (beta 2 GPI) molecule, one of the target autoantigens in APS, have linked infection to the development of APS. Using a peptide phage library, it has been shown that target epitopes of beta 2 GPI share similarities with common infectious pathogens. Also, circulating anti-beta 2 GPI antibodies have been identified in the sera of patients with different infectious conditions, and have been associated with various clinical APS manifestations. Molecular mimicry as a key mechanism linking infection and APS has been demonstrated in experimental models. In these studies, APS was induced by immunization of mice to various microbial pathogens. Anti-beta 2 GPI titers were found to be especially high following immunization with Haemophilus influenzae, Neisseria gonorrheae or tetanus toxoid. These findings contribute greatly to the understanding of APS pathogenesis, as well as create new directions for therapy modalities, namely specific peptide toleragens and antimicrobial treatment.
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PMID:The infectious etiology of the antiphospholipid syndrome: links between infection and autoimmunity. 1632 92

Purpura fulminans is a rare complication of a coagulopathy or an infection. Haemophilus influenzae infection, which has decreased since the haemophilus influenzae type B vaccine was initiated, is an unusual initiating cause of purpura fulminans. This case is the first reported in the literature of an adult who developed purpura fulminans after Haemophilus influenzae sepsis. Her elevated beta2 glycoprotein 1 ratio may have contributed to the severity of her disease. Although rare, Haemophilus influenzae may precipitate purpura fulminans. Current therapy is directed at control of precipitating factors, removal of nonviable tissue, treatment of secondary infections, and physiologic support. There also is evidence that patients respond well to hyperbaric oxygen therapy, with decreasing limb and tissue loss.
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PMID:Purpura fulminans in an adult patient with Haemophilus influenzae sepsis: case report and review of the literature. 1656 45

Respiratory syncytial virus (RSV) infection is associated with secondary bacterial infections caused by nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae. The pathogenesis of these complications is not completely understood; however, viral infection of respiratory epithelial cells promotes colonization by these bacteria. In the present study, RSV virions associated with NTHi and pneumococci in an inoculum-dependent manner in a fluid-phase binding assay. Adherence of NTHi and S. pneumoniae to epithelial cells transiently expressing RSV G glycoprotein was 2- and 2.2-fold higher, respectively, than adhesion to cells transfected with the vector alone (P <0.01). Furthermore, 4.6- and 6.2-fold larger numbers of NTHi and pneumococci bound to cells expressing a membrane-bound full-length RSV G protein than to cells expressing a truncated non-membrane-bound protein (P <or=0.005). Pre-incubating cells expressing membrane-bound G protein with blocking anti-RSV G antibodies reduced bacterial adherence by 78-84 % (P <or=0.005). These studies demonstrate that RSV G protein is a receptor for both NTHi and S. pneumoniae. Strategies to prevent this interaction may reduce the incidence of secondary bacterial complications of RSV infection.
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PMID:Nontypeable Haemophilus influenzae and Streptococcus pneumoniae bind respiratory syncytial virus glycoprotein. 1776 73


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