Inhibition of classical pathway activation by human neutrophil defensions

Berg, R.H. van den; Faber-Krol, Maria C.; Wetering, Sandra van; Hiemstra, Pieter S.; Daha, Mohamed R.

doi:10.1016/s0161-5890(98)90548-x

Cited by 19 publications

(22 citation statements)

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“…In accordance with the notion that defensins are capable of inducing the maturation/activation of antigen-presenting cells, enhanced antigen-specific humoral and cellular immune responses were found when antigen was administered in combination with HNP or mouse-homologues of beta-defensins [12,26]. Furthermore, defensins were demonstrated to inhibit the classic and lectin pathway of complement activation by binding C1q and mannose-binding lectin [29,30], they increase proliferation, migration, and proinflammatory cytokine secretion in keratinocytes [31][32][33], and enhance antigen-presentation and proinflammatory cytokine secretion in lung epithelial cells [27,[34][35][36]. enhancing antigen-specific humoral and cellular immune response HNP [12,26] Legend Our current understanding of inciting events in autoimmune disorders such as systemic lupus erythematosus or rheumatoid arthritis crucially involves presentation of autoantigens by antigen-presenting cells to T-cells which subsequently promote adaptive immune responses including the generation of autoantibodies.…”

Section: Immunomodulatory Effect Of Defensinssupporting

confidence: 64%

Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

Vordenbäumen

Schneider

2011

Polymers

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Abstract:Defensins are small cationic peptides with antimicrobial properties. They constitute a highly conserved innate immune defense mechanism across species. Based on the arrangement of disulfide-bonds, α-and β-defensins are distinguished in humans. Both types of defensin comprise several distinct molecules that are preferentially expressed at epithelial surfaces and in blood cells. In the last decade, multiple immunomodulatory functions of defensins have been recognized, including chemotactic activity, the promotion of antigen presentation, and modulations of proinflammatory cytokine secretion. These findings suggested a role for defensins not only as a first line of defense, but also as connectors of innate and adaptive immune responses. Recently, increasingly accumulating evidence has indicated that defensins may also be involved in the pathogenesis of autoimmune rheumatic disorders such as systemic lupus erythematosus and rheumatoid arthritis. The current review summarizes the data connecting defensins to autoimmunity.

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Section: Immunomodulatory Effect Of Defensinssupporting

confidence: 64%

Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

Vordenbäumen

Schneider

2011

Polymers

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“…In addition to their direct antimicrobial activities, defensins have a variety of other activities relevant to innate or adaptive immunity. HNPs inhibit complement activation, through interaction with the collagen domain of C1q (34). Defensins have chemotactic activity for monocytes, T cells, and dendritic cells, stimulate IL-8 production by epithelial cells, bind to lipid bilayers, and contribute to respiratory cell activation, injury or growth under some circumstances (35)(36)(37)(38)(39)(40)(41).…”

Section: Nfluenza a Virus (Iav)mentioning

confidence: 99%

Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

Hartshorn

White

Tecle

et al. 2006

The Journal of Immunology

111

115

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Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection, in part by modifying interactions with neutrophils. Human neutrophil defensins (HNPs) inhibit infectivity of enveloped viruses, including IAV. Our goal in this study was to characterize antiviral interactions between SP-D and HNPs. Recombinant and/or natural forms of SP-D and related collectins and HNPs were tested for antiviral activity against two different strains of IAV. HNPs 1 and 2 did not inhibit viral hemagglutination activity, but they interfered with the hemagglutination-inhibiting activity of SP-D. HNPs had significant viral neutralizing activity against divergent IAV strains. However, the HNPs generally had competitive effects when combined with SP-D in assays using an SP-D-sensitive IAV strain. In contrast, cooperative antiviral effects were noted in some instances when relatively SP-D-resistant strains were treated with SP-D and HNPs. HNPs were found to bind to the neck and/or carbohydrate recognition domain of SP-D. This binding was specific because no, or minimal, binding to other collectins was found. HNPs precipitated SP-D from bronchoalveolar lavage fluid and reduced the antiviral activity of bronchoalveolar lavage fluid. HNP-1 and -2 differed somewhat in their independent antiviral activity and their binding to SP-D. These results are relevant to the early phase of host defense against IAV, and suggest a complex interplay between SP-D and HNPs at sites of active inflammation.

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“…In addition to their microbicidal activity, defensins also are chemotactic for monocytes, T lymphocytes, and dendritic cells [22,118,126]; inhibit the binding of ACTH to its receptors (hence the name "corticostatins") [119]; suppress the activation of the classical pathway of complement [121]; induce histamine release from mast cells [14]; and promote the binding of lipoprotein(a) to the vascular matrix [13,54]. All defensins are polycationic peptides of 3-5 kDa and are characterized by the presence of six or eight conserved cysteine residues forming three or four intramolecular disulfide bridges.…”

Section: Defensins a Superfamily Of Conserved Cysteine-rich Ampsmentioning

confidence: 99%

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

Zhang¹,

Ross²,

Blecha³

2000

Vet. Res.

109

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-Antimicrobial peptides (AMPs) are small, endogenous, polycationic molecules that constitute a ubiquitous and significant component of innate immunity. These natural antibiotics have broad microbicidal activity against various bacteria, fungi, and enveloped viruses. Because most AMPs kill bacteria by physical disruption of cell membranes, which may prevent microorganisms from developing resistance against these agents, they are being explored as possible alternatives to conventional antibiotics. Pigs, like many other mammals, produce an impressive array of AMPs, which are synthesized predominantly by host leukocytic phagocytes or mucosal epithelial cells. Currently, more than a dozen distinct porcine AMPs have been identified and a majority belongs to the cathelicidin family. This review briefly summarizes recent advances in porcine AMP research with an emphasis on the diverse biological functions of each peptide. Mechanisms of action of these AMPs and their role in the resistance to infections are considered. Finally, the current status of pharmaceutical and agricultural uses of AMPs as well as future prospects for their application in the food animal industry is discussed.pig / antimicrobial peptide / cathelicidin / defensin / innate immunity Résumé -Peptides antimicrobiens porcins : nouvelles perspectives pour d'anciennes molécules de défense de l'hôte. Les peptides antimicrobiens sont de petites molécules endogènes, polycationiques, qui représentent un élément important et ubiquitaire des défenses immunes naturelles. Ces antibiotiques naturels ont un effet antimicrobien à large spectre, à la fois contre des bactéries, des moisissures et des virus enveloppés. Comme la plupart de ces peptides antimicrobiens tuent les bactéries par altération physique de leur membrane, ce qui peut éviter le développement de souches microbiennes résistantes à ces agents, ils représentent des alternatives possibles à l'emploi des antibiotiques classiques. Le porc, comme de nombreux autres mammifères, produit une gamme importante de peptides antimicrobiens, synthétisés pour l'essentiel par les leucocytes à activité phagocytaire, ou par les cellules épithéliales des muqueuses. Il y a actuellement plus d'une douzaine de peptides antimicrobiens identifiés chez le porc, dont la majorité fait partie de la famille des cathélicidines. Cet article résume les progrès récents accomplis dans le domaine des peptides antimicrobiens du porc, Vet. Res. 31 (2000) 277-296 277

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Inhibition of classical pathway activation by human neutrophil defensions

Cited by 19 publications

References 0 publications

Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

Innate Defense against Influenza A Virus: Activity of Human Neutrophil Defensins and Interactions of Defensins with Surfactant Protein D

Porcine antimicrobial peptides: New prospects for ancient molecules of host defense

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