Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis

Olofsson, A M; Vestberg, Mikael; Herwald, Heiko; Rygaard, Jørgen; Gourichon, David; Arfors, K. E.; Linde, Viggo; Flodgaard, Hans; Dedio, Jürgen; Müller‐Esterl, Werner; Lundgren-Åkerlund, Evy

doi:10.1172/jci6671

Cited by 58 publications

(60 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We show that liberation of HBP and its consequent binding to the EC surface depends on integrin-mediated tight adhesion of PMN to EC, whereas the transient rolling interaction is insufficient in causing substantial HBP release. The accumulation of HBP on the endothelium is reduced by treatment with heparinase, indicating that the cationic nature of the protein favors binding to negatively charged proteoglycans in the endothelial glycocalyx (25). In response to treatment with TNF-␣ or LPS we found intracellular immunoreactivity for HBP, which is in agreement with findings by Lee et al (23).…”

Section: Discussionsupporting

confidence: 92%

Neutrophil-Derived Heparin-Binding Protein (HBP/CAP37) Deposited on Endothelium Enhances Monocyte Arrest under Flow Conditions

Soehnlein

Xie²,

Ulbrich³

et al. 2005

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

In acute inflammation, infiltration of neutrophils often precedes a second phase of monocyte invasion, and data in the literature suggest that neutrophils may directly stimulate mobilization of monocytes via neutrophil granule proteins. In this study, we present a role for neutrophil-derived heparin-binding protein (HBP) in monocyte arrest on endothelium. Adhesion of neutrophils to bovine aorta endothelial cells (ECs) or HUVEC-triggered secretion of HBP and binding of the protein to the EC surface. Blockade of neutrophil adhesion by treatment with a mAb to CD18 greatly reduced accumulation of HBP. In a flow chamber model, immobilized recombinant HBP induced arrest of human monocytes or monocytic Mono Mac 6 (MM6) cells to activated EC or plates coated with recombinant adhesion molecules (E-selectin, P-selectin, VCAM-1). However, immobilized recombinant HBP did not influence arrest of neutrophils or lymphocytes. Treatment of MM6 cells with recombinant HBP evoked a rapid and clear-cut increase in cytosolic free Ca2+ that was found to be critical for the HBP-induced monocyte arrest inasmuch as pretreatment with the intracellular calcium chelating agent BAPTA-AM abolished the evoked increase in adhesion. Thus, secretion of a neutrophil granule protein, accumulating on the EC surface and promoting arrest of monocytes, could contribute to the recruitment of monocytes at inflammatory loci.

show abstract

Section: Discussionsupporting

confidence: 92%

Neutrophil-Derived Heparin-Binding Protein (HBP/CAP37) Deposited on Endothelium Enhances Monocyte Arrest under Flow Conditions

Soehnlein

Xie²,

Ulbrich³

et al. 2005

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, it was reported from various studies that HSPGs have a putative role in the binding and translocation of hydrophobic molecules (Al-Haideri et al, 1997;Boyd et al, 1998;Mulder and Terwel, 1998;Wells and Blajchman, 1998). Furthermore, it was reported that HSPGs, such as syndecans and glypicans, are involved in binding, cellular uptake and perinuclear vesicular compartmentalization of a heparin-binding protein (HBP) in endothelial cells, and, as a consequence, in cellular protection from apoptosis (Olofsson et al, 1999). Whether GPC3 is involved in such a translocation or compartmentalization process of antitumour agents has to be elicited in further investigations.…”

Section: Discussionmentioning

confidence: 99%

Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells

et al. 2003

View full text Add to dashboard Cite

Elevated expression of the heparan sulphate proteoglycan glypican-3 (GPC3) was found on mRNA and protein levels in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV, which was established by in vitro selection against mitoxantrone. In order to elucidate a putative role of GPC3 in the drug-resistant phenotype, the mitoxantrone-resistant cell line EPG85-257RNOV was transfected with an expression vector construct carrying an anti-GPC3 hammerhead ribozyme. It could be demonstrated that in anti-GPC3 ribozymetransfected cell clones, the GPC3-specific mRNA and corresponding protein expression levels were decreased to levels that are similar to those observed in nonresistant, parental cells. The anti-GPC3 ribozyme-containing clones reduced the mitoxantrone resistance level up to 21% of the original resistance and the crossresistance against etoposide to 33% of the original value. This reversal of drug resistance was accompanied by an increased cellular mitoxantrone accumulation in the anti-GPC3 ribozymeexpressing cells. In conclusion, it was verified that GPC3 is involved in the cellular protection against mitoxantrone in the atypical multidrug-resistant gastric carcinoma cell line EPG85-257RNOV. Oncogene (2004) 23, 945-955.

show abstract

“…Interestingly, azurocidin is only deposited by adherent but not rolling PMN, indicating that PMN activation via ␤ 2 -integrins is an important signal for discharge of secretory vesicles. The accumulation of azurocidin on the endothelium is reduced by treatment with heparinase and chondroitinase, suggesting that negatively charged proteoglycans in the endothelial glycocalyx act as primary binding sites [23,24]. A specific receptor for azurocidin on EC has not been identified.…”

Section: Azurocidin Induces Recruitment Of Monocytesmentioning

confidence: 99%

Neutrophil-derived azurocidin alarms the immune system

Soehnlein

Lindbom

2008

Journal of Leukocyte Biology

View full text Add to dashboard Cite

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.

show abstract

Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis

Cited by 58 publications

References 45 publications

Neutrophil-Derived Heparin-Binding Protein (HBP/CAP37) Deposited on Endothelium Enhances Monocyte Arrest under Flow Conditions

Neutrophil-Derived Heparin-Binding Protein (HBP/CAP37) Deposited on Endothelium Enhances Monocyte Arrest under Flow Conditions

Glypican-3 is involved in cellular protection against mitoxantrone in gastric carcinoma cells

Neutrophil-derived azurocidin alarms the immune system

Contact Info

Product

Resources

About