Neutrophil primary granule proteins HBP and HNP1–3 boost bacterial phagocytosis by human and murine macrophages

Soehnlein, Oliver; Kai-Larsen, Ylva; Frithiof, Robert; Sorensen, Ole E.; Kenne, Ellinor; Scharffetter‐­Kochanek, Karin; Eriksson, Einar E.; Herwald, Heiko; Agerberth, Birgitta; Lindbom, Lennart

doi:10.1172/jci35740

Cited by 187 publications

(173 citation statements)

References 42 publications

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“…Recently, azurocidin was identified as an activator of human macrophages, as demonstrated not only by intracellular Ca 2ϩ mobilization but also by a change in the phenotype [44]. Treatment of macrophages with azurocidin enhanced the expression of HLA II, CD40, and CD86, in agreement with findings from microglial cells treated similarly [45].…”

Section: Azurocidin Activates Monocytes and Macrophagessupporting

confidence: 73%

“…In this study, PMN-derived azurocidin activates macrophages via ␤ 2 -integrins, which causes release of TNF-␣ and IFN-␥ [44,52]. As a consequence, CD64 and CD32 are up-regulated.…”

Section: Azurocidin Enhances Bacterial Phagocytosismentioning

confidence: 74%

“…Expression of these molecules is a sign of the classical macrophage activation being functionally related to enhanced antimicrobial effectiveness and a more powerful activation of the adaptive immune system [46]. Furthermore, Fc␥Rs CD64 and CD32 are up-regulated in response to treatment with azurocidin but not [44]. More importantly, they were not only secreted from the macrophage in response to azurocidin, but they were also found to be responsible for the macrophage activation pattern.…”

Section: Azurocidin Activates Monocytes and Macrophagesmentioning

confidence: 99%

“…As discussed earlier, immobilized azurocidin enhances the adhesion of monocytes to EC, a response that could be blocked as well with an antibody to CD18 (unpublished observation). Similarly, release of TNF-␣ and IFN-␥ from macrophages and enhanced Fc␥R expression on macrophages in response to azurocidin can be inhibited by treatment with a CD18 antibody [44]. In addition, Ca 2ϩ mobilization in macrophages was inhibited by herbimycin, a tyrosine kinase inhibitor, underlining the ␤ 2 -integrins to be of major importance in the azurocidin-monocyte interaction [44].…”

Section: Azurocidin Mediates Its Effects On Leukocytes Via ␤ 2 -Integmentioning

confidence: 99%

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Neutrophil-derived azurocidin alarms the immune system

Soehnlein

Lindbom

2008

Journal of Leukocyte Biology

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102

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Azurocidin (heparin-binding protein/ cationic antimicrobial protein of 37 kD) is a protein that is mobilized rapidly from emigrating polymorphonuclear leukocytes (PMN). Initially, this inactive serine protease was recognized for its antimicrobial effects. However, it soon became apparent that azurocidin may act to alarm the immune system in different ways and thus serve as an important mediator during the initiation of the immune response. Azurocidin, released from PMN secretory vesicles or primary granules, acts as a chemoattractant and activator of monocyte and macrophages. The functional consequence is enhancement of cytokine release and bacterial phagocytosis, allowing for a more efficient bacterial clearance. Leukocyte activation by azurocidin is mediated via ␤ 2 -integrins, and azurocidin-induced chemotaxis is dependent on formyl-peptide receptors. In addition, azurocidin activates endothelial cells leading to vascular leakage and edema formation. For these reasons, targeting azurocidin release and its actions may have therapeutic potential in inflammatory disease conditions. J. Leukoc. Biol. 85: 344 -351; 2009.

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Section: Azurocidin Activates Monocytes and Macrophagessupporting

confidence: 73%

“…In this study, PMN-derived azurocidin activates macrophages via ␤ 2 -integrins, which causes release of TNF-␣ and IFN-␥ [44,52]. As a consequence, CD64 and CD32 are up-regulated.…”

Section: Azurocidin Enhances Bacterial Phagocytosismentioning

confidence: 74%

Section: Azurocidin Activates Monocytes and Macrophagesmentioning

confidence: 99%

Section: Azurocidin Mediates Its Effects On Leukocytes Via ␤ 2 -Integmentioning

confidence: 99%

See 2 more Smart Citations

Neutrophil-derived azurocidin alarms the immune system

Soehnlein

Lindbom

2008

Journal of Leukocyte Biology

Self Cite

102

100

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“…CD64 is a leukocyte glycoprotein receptor that mediates phagocytosis of microbes opsonized by IgG (28), thereby eliciting phagocyte production of microbicidal reactive oxygen species (ROS). Recent studies by Soehnlein et al demonstrated that macrophage CD64 is up-regulated by neutrophil azurocidin (29). Although resting neutrophils generally express low levels of CD64 at the plasma membrane, surface expression increases following activation by proinflammatory stimuli (28).…”

Section: Short-term Changes In the Host Transcriptional Response To Gasmentioning

confidence: 99%

Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus

Shea

Virtaneva

Kupko

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Relatively little is understood about the dynamics of global hostpathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a distinct host transcriptome response, we performed genome-wide transcriptome analysis using a nonhuman primate model of experimental pharyngitis. We also identified host and pathogen biological processes and individual host and pathogen gene pairs with correlated patterns of expression, suggesting interaction. For this study, 509 host genes and seven biological pathways were differentially expressed throughout the entire 32-day infection cycle. GAS infection produced an initial widespread significant decrease in expression of many host genes, including those involved in cytokine production, vesicle formation, metabolism, and signal transduction. This repression lasted until day 4, at which time a large increase in expression of host genes was observed, including those involved in protein translation, antigen presentation, and GTP-mediated signaling. The interactome analysis identified 73 host and pathogen gene pairs with correlated expression levels. We discovered significant correlations between transcripts of GAS genes involved in hyaluronic capsule production and host endocytic vesicle formation, GAS GTPases and host fibrinolytic genes, and GAS response to interaction with neutrophils. We also identified a strong signal, suggesting interaction between host γδ T cells and genes in the GAS mevalonic acid synthesis pathway responsible for production of isopentenyl-pyrophosphate, a short-chain phospholipid that stimulates these T cells. Taken together, our results are unique in providing a comprehensive understanding of the host-pathogen interactome during mucosal infection by a bacterial pathogen.epithelial growth factor receptor | host pathogen | microarray | Streptococcus pyogenes | transcriptome

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Involvement of HNP‐1 in different oxidation mechanisms in human endothelial cells

Ping

et al. 2010

Euro J Lipid Sci & Tech

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The objective of this study was to elucidate the different mechanisms of low-density lipoprotein (LDL) oxidation by human endothelial cells. High level of LDL stimulated human alpha-defensin 1 (HNP-1) expression strongly, activated myeloperoxidase (MPO), and accumulated malondialdehyde (MDA). In addition, lipopolysaccharides (LPS) had similar effect, however the cell response occurred even earlier.After 12 h of LDL co-culture, the cells were washed and fresh LDL was added again. MPO activity and MDA generation were increased. Adding fresh LDL after the LPS co-culture for 3 h, a similar trend, however weaker effect was observed. Culturing cells with LDL and adding various kinds of calcium antagonists at the same time did not make obvious changes to the expression of HNP-1. In contrast, culturing cells with LPS, calcium antagonists increased HNP-1 expression. Adding the anti-radical drug sodium ferulate had no significant effect on oxidative function activated by LDL, but the oxidation activated by LPS was suppressed significantly and the HNP-1 expression was not changed significantly. The endogenous irritant LDL and the exogenous irritant LPS activated human endothelial cells in different manners and HNP-1 expression changes were involved.

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Neutrophil primary granule proteins HBP and HNP1–3 boost bacterial phagocytosis by human and murine macrophages

Cited by 187 publications

References 42 publications

Neutrophil-derived azurocidin alarms the immune system

Neutrophil-derived azurocidin alarms the immune system

Interactome analysis of longitudinal pharyngeal infection of cynomolgus macaques by group A Streptococcus

Involvement of HNP‐1 in different oxidation mechanisms in human endothelial cells

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