Complement activation in the nasal mucosa following nasal ragweed‐allergen challenge

Mezei, G; Varga, Lilian; Veres, Amarilla; Füst, George; Cserháti, E

doi:10.1034/j.1399-3038.2001.012004201.x

Cited by 12 publications

(11 citation statements)

References 15 publications

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“…Complement activation at the nasal mucosa has been described in immediate allergic reaction to pollens (birch and Timothy grass pollen), culminating in the generation of ATs [18]. Ragweed allergen challenge also promotes the generation of C3 degradation products in the nasal mucosa of adolescents with AR [19]. Complement receptor 3 (CR3) is expressed together with Toll-like receptors (TLRs) in human sinonasal tissues [20].…”

Section: Complement Activation In Allergic Airway Diseasesmentioning

confidence: 99%

The Role of Complement in the Diagnosis and Management of Allergic Rhinitis and Allergic Asthma

Laumonnier

Schmudde

Köhl

2010

Curr Allergy Asthma Rep

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Allergic rhinitis and asthma are common chronic inflammatory diseases of the nasal mucus membranes and the upper airways with a high prevalence in Western countries. In addition to maladaptive T-helper type 2 (Th2) immunity, Th17 cells can drive the inflammatory responses in both diseases. Several reports have shown that the complement system is activated locally and systemically in allergic rhinitis and/or allergic asthma patients. Importantly, recent findings in experimental models of allergic rhinitis and allergic asthma suggest that the complement cleavage products complement 3a and complement 5a and the activation of their corresponding receptors in antigen-presenting cells regulate the development of maladaptive Th2 and Th17 immunity. These findings in experimental asthma are corroborated by genome-wide searches and candidate gene studies in humans. We discuss recent findings in experimental and human allergic airway diseases suggesting that complement may serve as a new diagnostic and therapeutic target for both disorders.

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Section: Complement Activation In Allergic Airway Diseasesmentioning

confidence: 99%

The Role of Complement in the Diagnosis and Management of Allergic Rhinitis and Allergic Asthma

Laumonnier

Schmudde

Köhl

2010

Curr Allergy Asthma Rep

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“…The boosted level of serum resistance seen with encapsulated strains that bind fH could be critical for bacterial survival in the bloodstream, where high levels of complement are present. Although bacteria at mucosal surfaces encounter lower levels of complement (54), colonizing meningococci (which are often unencapsulated and potentially more serum sensitive) need to evade complement to successfully inhabit the nasopharynx.…”

Section: Discussionmentioning

confidence: 99%

The Meningococcal Vaccine Candidate GNA1870 Binds the Complement Regulatory Protein Factor H and Enhances Serum Resistance

Madico

Welsch²,

Lewis

et al. 2006

The Journal of Immunology

364

432

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Neisseria meningitidis binds factor H (fH), a key regulator of the alternative complement pathway. A ∼29 kD fH-binding protein expressed in the meningococcal outer membrane was identified by mass spectrometry as GNA1870, a lipoprotein currently under evaluation as a broad-spectrum meningococcal vaccine candidate. GNA1870 was confirmed as the fH ligand on intact bacteria by 1) abrogation of fH binding upon deleting GNA1870, and 2) blocking fH binding by anti-GNA1870 mAbs. fH bound to whole bacteria and purified rGNA1870 representing each of the three variant GNA1870 families. We showed that the amount of fH binding correlated with the level of bacterial GNA1870 expression. High levels of variant 1 GNA1870 expression (either by allelic replacement of gna1870 or by plasmid-driven high-level expression) in strains that otherwise were low-level GNA1870 expressers (and bound low amounts of fH by flow cytometry) restored high levels of fH binding. Diminished fH binding to the GNA1870 deletion mutants was accompanied by enhanced C3 binding and increased killing of the mutants. Conversely, high levels of GNA1870 expression and fH binding enhanced serum resistance. Our findings support the hypothesis that inhibiting the binding of a complement down-regulator protein to the neisserial surface by specific Ab may enhance intrinsic bactericidal activity of the Ab, resulting in two distinct mechanisms of Ab-mediated vaccine efficacy. These data provide further support for inclusion of this molecule in a meningococcal vaccine. To reflect the critical function of this molecule, we suggest calling it fH-binding protein.

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“…Human antibody and complement play important roles in controlling the spread of the pathogen, such that in most individuals, the bacterium remains confined to respiratory mucosa (Nicholson and Lepow, 1979; Ross and Densen, 1984; Figueroa et al ., 1993). However, in this environment also, the bacterium may encounter human antibody, complement factors and other serum proteins (Pohl et al ., 1991; Rautemaa and Meri, 1996; Mezei et al ., 2001). One mechanism, by which meningococci may acquire a level of resistance to antibody and complement‐mediated killing, is by sequestration of complement control factors such as factor H (fH), complement component C4 binding protein (C4BP) and/or vitronectin (Vn).…”

Section: Introductionmentioning

confidence: 99%

Meningococcal surface fibril (Msf) binds to activated vitronectin and inhibits the terminal complement pathway to increase serum resistance

Griffiths¹,

Hill²,

Borodina³

et al. 2011

Molecular Microbiology

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SummaryComplement evasion is an important survival strategy of Neisseria meningitidis (Nm) during colonization and infection. Previously, we have shown that Nm Opc binds to serum vitronectin to inhibit complementmediated killing. In this study, we demonstrate meningococcal interactions with vitronectin via a novel adhesin, Msf (meningococcal surface fibril, previously NhhA or Hsf). As with Opc, Msf binds preferentially to activated vitronectin (aVn), engaging at its N-terminal region but the C-terminal heparin binding domain may also participate. However, unlike Opc, the latter binding is not heparin-mediated. By binding to aVn, Msf or Opc can impart serum resistance, which is further increased in coexpressers, a phenomenon dependent on serum aVn concentrations. The survival fitness of aVn-binding derivatives was evident from mixed population studies, in which msf/opc mutants were preferentially depleted. In addition, using vitronectin peptides to block Msf-aVn interactions, aVninduced inhibition of lytic C5b-9 formation and of serum killing could be reversed. As Msf-encoding gene is ubiquitous in the meningococcal strains examined and is expressed in vivo, serum resistance via Msf may be of significance to meningococcal pathogenesis. The data imply that vitronectin binding may be an important strategy for the in vivo survival of Nm for which the bacterium has evolved redundant mechanisms.

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Complement activation in the nasal mucosa following nasal ragweed‐allergen challenge

Cited by 12 publications

References 15 publications

The Role of Complement in the Diagnosis and Management of Allergic Rhinitis and Allergic Asthma

The Role of Complement in the Diagnosis and Management of Allergic Rhinitis and Allergic Asthma

The Meningococcal Vaccine Candidate GNA1870 Binds the Complement Regulatory Protein Factor H and Enhances Serum Resistance

Meningococcal surface fibril (Msf) binds to activated vitronectin and inhibits the terminal complement pathway to increase serum resistance

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