Neutrophil-derived azurocidin alarms the immune system

Soehnlein, Oliver; Lindbom, Lennart

doi:10.1189/jlb.0808495

Cited by 102 publications

(105 citation statements)

References 77 publications

(85 reference statements)

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“…b2-integrins are localised in secretory vesicles, a compartment discharged when neutrophil-endothelial interaction is established. Secretory vesicles are also rich in azurocidin [29], a protein previously associated with neutrophil-mediated permeability changes [5,30,31]. Hence, reduced surface-expression of b2-integrins following fMLP stimulation not only explains reduced adhesive capacity, but may also point to impaired release of granule proteins relevant to ALI.…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

2012

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Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Activation and recruitment of neutrophils are regarded as key mechanisms in the progression of ALI. As pioglitazone holds potent pleiotropic anti-inflammatory effects, we explored its effects during ALI.C57Bl/6 mice were exposed to aerosolised lipopolysaccharides (LPSs) (500 mg?mL) and their alveolar, interstitial and intravascular neutrophils were assessed 4 h later. Lung permeability changes were evaluated by fluorescein isothiocyanate-dextran clearance and protein content in the bronchoalveolar lavage fluid. In vitro, human isolated neutrophils were pretreated with piolitazone (10 mM, for 1 or 3 h) and then activated with N-formyl-L-methionyl-L-leucyl-Lphenylalanine. Neutrophil activation, adhesion, release and formation of reactive oxygen species (ROS) and phagocytosis were measured thereafter.Pioglitazone treatment before or after induction of ALI significantly diminished alveolar (reduction by 73% and 67%, respectively) and interstitial neutrophil influx (reduction by 55% and 63%, respectively) and reduced lung permeability changes (reduction by 64% and 58%, respectively) indicating a protective role of pioglitazone treatment in ALI. Moreover, pioglitazone significantly reduced degranulation and adhesion of neutrophils without affecting ROS formation and release or bacterial phagocytosis.Pioglitazone reduces recruitment and activation of neutrophils thereby preventing LPS-induced ALI. Our results imply a potential role for pioglitazone treatment in the management of ALI.

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Section: Discussionmentioning

confidence: 99%

Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

2012

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“…Furthermore, neutrophil granule components like cathepsin G or azurocidin also attract monocytes [81]. Azurocidin exerts its recruitment effect directly through β 2 integrins or indirectly through endothelial cells and activates macrophages to release neutrophil degranulating cytokines, completing a feedback amplification loop [82] ( Figure 4C). Activated macrophages can also release matrix metalloproteinases [83] such as MMP8 and MMP9, which promote neutrophil chemotaxis by proteolytic activation of CXCL5 and CXCL8 [73,84].…”

Section: Amplification Of Neutrophil Function Through Other Immune Cellsmentioning

confidence: 99%

Feedback Amplification of Neutrophil Function

Németh

Mócsai

2016

Trends in Immunology

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“…Besides its direct antimicrobial properties, azurocidin has been recognized as a mediator during the initiation of the immune response. 78 Unlike the other serprocidins, azurocidin is not only stored in the azurophil granules but also in the secretory granules and therefore partly released at a very early stage of extravasation. Its specific regulatory effects include the recruitment and activation of monocytes leading to enhanced cytokine release and phagocytotic activity.…”

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Antimicrobial peptides: The ancient arm of the human immune system

Wiesner¹,

Vilcinskas²

2010

Virulence

611

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The production of peptides and small proteins with microbicidal activity collectively called antimicrobial peptides (AMPs) is commonly considered to be a primitive mechanism of immunity and has been extensively studied in insects and other non-vertebrate organisms. In addition, a variety of AMPs present in amphibian skin secretion has been well characterised. There is now increasing evidence that AMPs play a crucial role in human immunity as well. Virtually all human tissues and cells typically exposed to microbes are able to produce AMPs. Important AMPs belonging to two structurally distinct classes, known as the defensins and the cathelicidins, are mainly produced by epithelial cells and neutrophils. AMPs significantly contributing to the chemical skin barrier are represented by dermcidin, psoriasin and RNase 7. The antimicrobial activity of saliva largely depends on histidine-rich AMPs known as histatins. Many more, in part less well-known AMPs and AMP-like proteins exist that exhibit various additional functions, apart from their antimicrobial properties. Among them, the neutrophil granule proteins azurocidin and cathepsin G are members of a family of serine-protease homologues called serprocidins and play a role in the regulation of the immune response and degradation of extracellular matrix proteins respectively. As another AMP-like protein of the neutrophil granule content, bactericidal/permeability increasing protein (BPI) is both able to permeabilise bacterial membranes and to function as an opsonin. The whey acidic protein (WAP) domain containing class of AMPs, including secretory leukocyte protease inhibitor (SLPI), elafin and trappin-2, is equally important in inhibition of neutrophil serine proteases and killing of microbes. Certain CC or CXC chemokines are known to possess antimicrobial properties and therefore are called kinocidins. Several kinocidins, including thrombocidin-1 and -2, are contained in the ?-granules of platelets. A cytoplasmic AMP described as ubiquicidin turned out to be identical with the strongly basic ribosomal protein S30. Proteolytic cleavage of the histone protein H2A in the stomach gives rise to an AMP initially described as buforin I. Adrenomedullin is a hormone-like AMP exhibiting vasodilatory and hypotensive effects. Lysozyme is mainly known for its cell wall degrading activity, but is also capable of non-enzymatic killing of bacteria. An iron-binding protein present in milk and other secretions named lactoferrin was shown to possess antimicrobial and antiviral activity and has been implicated in protection against cancer. Clinical studies on the treatment of infectious diseases have been performed with artificial peptides derived from human lactoferrin, histatins and BPI in addition to porcine protegrins, frog magains and bovine indolicidin. Omiganan, representing an indolicidin derivative, has been demonstrated to be effective in the treatment of acne and catheter-related local infections and is currently considered to be the most promising AMP-based drug candidate

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Neutrophil-derived azurocidin alarms the immune system

Cited by 102 publications

References 77 publications

Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

Pioglitazone attenuates endotoxin-induced acute lung injury by reducing neutrophil recruitment

Feedback Amplification of Neutrophil Function

Antimicrobial peptides: The ancient arm of the human immune system

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