Inhibition of Activation of the Classical Pathway of Complement by Human Neutrophil Defensins

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

doi:10.1182/blood.v92.10.3898.422k03_3898_3903

Cited by 52 publications

(19 citation statements)

References 36 publications

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“…Due to their abundance in neutrophilic granulocytes, they were termed human neutrophil defensins (HNPs). 5 including antiviral activity [6][7][8][9] Chemo-attracts monocytes, T-cells and dendritic cells [11][12][13][14] Inhibition of complement activation 223,224 Activation of mast cells 67…”

Section: Human Neutrophil α α-Defensin Peptides (Hnps 1-4)mentioning

confidence: 99%

Review: Human antimicrobial proteins — effectors of innate immunity

Harder

Gläser

Schröder

2007

Journal of Endotoxin Research

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We live in a world populated by an enormous number of micro-organisms. This necessitates the existence of highly effective mechanisms to control microbial growth. Through many research efforts, a chemical defense system based on the production of antimicrobial proteins (AMPs) has been identified. AMPs are endogenous, small proteins exhibiting antimicrobial activity against a wide variety of micro-organisms. The wide distribution of these molecules in the plant and animal kingdom reflects their biological significance. Various human AMPs show a potent effect on pathogenic micro-organisms including antibiotic-resistant bacteria. Thus, there is great interest in understanding the role of AMPs within innate immunity and evaluating their use and/or specific induction to fend off infections. In this review, we provide an overview of the characteristics of human AMPs and discuss examples where AMPs may be involved in the pathogenesis of infectious and inflammatory diseases.

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Section: Human Neutrophil α α-Defensin Peptides (Hnps 1-4)mentioning

confidence: 99%

Review: Human antimicrobial proteins — effectors of innate immunity

Harder

Gläser

Schröder

2007

Journal of Endotoxin Research

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“…Defensins may also participate in the immune response by causing neutrophil activation 201 and modulating the activity of the classical complement pathway by binding to complement C1q. 202,203 The aforementioned ability of defensins to inhibit adrenocorticotrophin activity, 180 and, therefore, reduce production of anti-inflammatory glucocorticoids, may also be a mechanism by which these peptides can enhance the immune response. Additionally, LL-37 is able to bind and neutralize lipopolysaccharide and lipotechoic acid, and, thus, reduce the inflammatory response associated with these molecules.…”

Section: Nonmicrobicidal Roles Of Defensins and Other Antimicrobiamentioning

confidence: 99%

Defensins and Other Antimicrobial Peptides at the Ocular Surface

McDermott

2004

The Ocular Surface

104

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Although constantly exposed to the environment and "foreign bodies" such as contact lenses and unwashed fingertips, the ocular surface succumbs to infection relatively infrequently. This is, in large part, due to a very active and robust innate immune response mounted at the ocular surface. Studies over the past 20 years have revealed that small peptides with antimicrobial activity are a major component of the human innate immune response system. The ocular surface is no exception, with peptides of the defensin and cathelicidin families being detected in the tear film and secreted by corneal and conjunctival epithelial cells. There is also much evidence to suggest that the role of some antimicrobial peptides is not restricted to direct killing of pathogens, but, rather, that they function in various aspects of the immune response, including recruitment of immune cells, and through actions on dendritic cells provide a link to adaptive immunity. A role in wound healing is also supported. In this article, the properties, mechanisms of actions and functional roles of antimicrobial peptides are reviewed, with particular emphasis on the potential multifunctional roles of defensins and LL-37 (the only known human cathelicidin) at the ocular surface.

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“…These peptides may further increase the production of tumor necrosis factor (TNF) and interleukin-1 (IL-1), and reduce the production of anti-inflammatory interleukin 10 (IL-10) [7,8]. Alpha-defensins act chemotactically on CD8 T lymphocytes, immature dendritic cells, and immature T lymphocytes, enhancing or suppressing activation of the classical complement pathway [9,10].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic significance of alpha-defensin in patients with chronic heart failure during 2-year follow-up

Banach¹,

Wołowiec²,

Rogowicz³

et al. 2018

Preprint

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BackgroundDefensins play an important role in the processes associated with innate immunity. Their growth is observed in sites of intense inflammation, but also in less severe inflammation. Evaluation of alpha-defensin levels in patients with chronic heart failure (CHF) and its possible association with a long-term prognosis may be an interesting supplement to knowledge about the state of the immune system in heart failure.The aim of the study was to compare the plasma concentration of alpha-defensin between the patients with chronic heart failure with impaired ventricular ejection fraction (LVEF) <45% and the control group, as well as to evaluate the prognostic value of alpha-defensin as a possible predictor of death during a 24-month observation period.Methods The study included 52 hospitalized patients with a primary diagnosis of CHF and LVEF <45%. 20 patients exhibited features of CHF exacerbation, the remaining 32 were hospitalized on schedule. The control group consisted of 28 healthy volunteers. The observation was conducted by telephone for 2 years. The end point of the study was death for all reasons.Results Patients with CHF had significantly higher levels of alpha-defensin than control subjects. Similarly, plasma hs-CRP levels were significantly higher in the study group than in the control group, although in both groups the median hs-CRP did not exceed 5 mg / L. It has not been shown that exacerbation has an effect on alpha-defensin concentration. During the two-year follow-up, statistically significant effects on the endpoint of the following parameters were observed: EF (p = 0.035, HR = 0.917), hs-CRP (p = 0.036; HR = 1.046) and NT-proBNP (p < 0.001, HR = 1.000078). ROC analysis showed that during both a 12-month (AUC = 0.333, p = 0.116) as well as a 24 month (AUC = 0.447, p = 0.616) observation period plasma concentration of alpha-defensin was not a good predictor of death in CHF patients.ConclusionsHigher levels of alpha-defensin in patients with CHF confirm subclinical inflammatory activation in this population. However, this marker does not have predictive value for predicting death in the medium-term observation.

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Inhibition of Activation of the Classical Pathway of Complement by Human Neutrophil Defensins

Cited by 52 publications

References 36 publications

Review: Human antimicrobial proteins — effectors of innate immunity

Review: Human antimicrobial proteins — effectors of innate immunity

Defensins and Other Antimicrobial Peptides at the Ocular Surface

Diagnostic and prognostic significance of alpha-defensin in patients with chronic heart failure during 2-year follow-up

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