Two Proteins Modulating Transendothelial Migration of Leukocytes Recognize Novel Carboxylated Glycans on Endothelial Cells

Srikrishna, Geetha; Panneerselvam, K.; Westphal, Vibeke; Abraham, Violet; Varki, Ajit; Freeze, Hudson H.

doi:10.4049/jimmunol.166.7.4678

Cited by 134 publications

(165 citation statements)

References 48 publications

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“…Recently, different compounds that also participate in the formation of extracellular matrix of connective tissue or basement lamina were found to associate with S100 proteins. For neutrophils, involvement of S100A8 and S100A9 in the modulation of transendothelial migration by interaction with glycosaminoglycans and carboxylated glycans has been shown (40,41). In addition, S100A8 and S100A9 have been described to increase adhesion of monocytes to fibronectin (42).…”

Section: Resultsmentioning

confidence: 99%

Calcium-Binding Proteins S100A8 and S100A9 as Novel Diagnostic Markers in Human Prostate Cancer

Hermani¹,

Heß

Servi³

et al. 2005

Clinical Cancer Research

222

158

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Purpose: S100 proteins comprise a family of calcium-modulated proteins that have recently been associated with epithelial tumors. We examined the expression of two members of this family, S100A8 and S100A9, together with the S100 receptor RAGE (receptor for advanced glycation end products) in human prostate adenocarcinomas and in prostatic intraepithelial neoplasia. Experimental Design:Tissue specimens of 75 patients with organ-confined prostate cancer of different grades were analyzed by immunohistochemistry for expression of S100A8, S100A9, and RAGE. In addition, in situ hybridization of S100A8 and S100A9 was done for 20 cases. An ELISA was applied to determine serum concentrations of S100A9 in cancer patients compared with healthy controls or to patients with benign prostatic hyperplasia (BPH). Results: S100A8, S100A9, and RAGE were up-regulated in prostatic intraepithelial neoplasia and preferentially in high-grade adenocarcinomas, whereas benign tissue was negative or showed weak expression of the proteins. There was a high degree of overlap of S100A8 and S100A9 expression patterns and of S100A8 or S100A9 and RAGE, respectively. Frequently, a gradient within the tumor tissue with an increased expression toward the invaded stroma of the prostate was observed. S100A9 serum levels were significantly elevated in cancer patients compared with BPH patients or healthy individuals. Conclusion: Our data suggest that enhanced expression of S100A8, S100A9, and RAGE is an early event in prostate tumorigenesis and may contribute to development and progression or extension of prostate carcinomas. Furthermore, S100A9 in serum may serve as useful marker to discriminate between prostate cancer and BPH.

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Section: Resultsmentioning

confidence: 99%

Calcium-Binding Proteins S100A8 and S100A9 as Novel Diagnostic Markers in Human Prostate Cancer

Hermani¹,

Heß

Servi³

et al. 2005

Clinical Cancer Research

222

158

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“…S100A8 and S100A9, induced in MEC by IL-1␤ and TNF in vitro (26), are observed in neovessels, but not larger vessels, in inflammatory lesions (15). The complex is deposited on the endothelium by transmigrating leukocytes; S100A9 binds endothelial cells (EC) via heparan sulfate proteoglycans (58) and to carboxylated N-glycans on activated EC (59). S100A8 has functions separate from those involving heterodimerization with S100A9 (60), and although we have not confirmed S100A8-SNO in EC, it may modulate microvascular function in inflamed vessels.…”

Section: Discussionmentioning

confidence: 99%

S-Nitrosylated S100A8: Novel Anti-Inflammatory Properties

Lim

Raftery

Cai

et al. 2008

The Journal of Immunology

109

106

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S100A8 and S100A9, highly expressed by neutrophils, activated macrophages, and microvascular endothelial cells, are secreted during inflammatory processes. Our earlier studies showed S100A8 to be an avid scavenger of oxidants, and, together with its dependence on IL-10 for expression in macrophages, we postulated that this protein has a protective role. S-nitrosylation is an important posttranslational modification that regulates NO transport, cell signaling, and homeostasis. Relatively few proteins are targets of S-nitrosylation. To date, no inflammation-associated proteins with NO-shuttling capacity have been identified. We used HPLC and mass spectrometry to show that S100A8 and S100A9 were readily S-nitrosylated by NO donors. S-nitrosylated S100A8 (S100A8-SNO) was the preferred nitrosylated product. No S-nitrosylation occurred when the single Cys residue in S100A8 was mutated to Ala. S100A8-SNO in human neutrophils treated with NO donors was confirmed by the biotin switch assay. The stable adduct transnitrosylated hemoglobin, indicating a role in NO transport. S100A8-SNO suppressed mast cell activation by compound 48/80; intravital microscopy was used to demonstrate suppression of leukocyte adhesion and extravasation triggered by compound 48/80 in the rat mesenteric microcirculation. Although S100A8 is induced in macrophages by LPS or IFN-γ, the combination, which activates inducible NO synthase, did not induce S100A8. Thus, the antimicrobial functions of NO generated under these circumstances would not be compromised by S100A8. Our results suggest that S100A8-SNO may regulate leukocyte-endothelial cell interactions in the microcirculation, and suppression of mast cell-mediated inflammation represents an additional anti-inflammatory property for S100A8.

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“…70) It was reported that calprotectin interacts with carboxylated glycan 71) or sulfated glycosamininoglycans 72) on endothelial cells. It was also proposed that a 2 -macroglobulin is a ligand on endothelial cells for calprotectin.…”

Section: Fig 2 Effect Of Calprotectin On the Growth Of Various Tumomentioning

confidence: 99%

Calprotectin (S100A8/S100A9), an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity

Yui

Nakatani

Mikami

2003

Biological & Pharmaceutical Bulletin

275

211

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Calprotectin, a complex of two calcium-binding proteins that belong to the S100 protein family, is abundant in the cytosolic fraction of neutrophils. A high level of calprotectin reportedly exists in extracellular fluid during various inflammatory conditions, such as rheumatoid arthritis, cystic fibrosis and abscesses. However, the exact biological role(s) of the factor is now under investigation. We recently observed that neutrophils contain a factor that shows growth-inhibitory and apoptosis-inducing activities against various cell types including tumor cells and normal fibroblasts, and we identified that factor as calprotectin. The findings suggest that calprotectin exerts a regulatory activity in inflammatory processes through its effect on the survival or growth states of cells participating in the inflammatory reaction. It is also possible that calprotectin, at a high concentration, might have a deleterious effect on fibroblasts and influence the recovery of inflammatory tissue. Therefore, the protein factor may be a new drug target to control inflammatory reactions. We found that a few of the Amaryllidaceae alkaloids effectively inhibited the growth-inhibitory and apoptosis-inducing activities of calprotectin. In this article, we focus on the biological functions of calprotectin in extracellular fluids, focusing on its apoptosis-inducing activity.

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Two Proteins Modulating Transendothelial Migration of Leukocytes Recognize Novel Carboxylated Glycans on Endothelial Cells

Cited by 134 publications

References 48 publications

Calcium-Binding Proteins S100A8 and S100A9 as Novel Diagnostic Markers in Human Prostate Cancer

Calcium-Binding Proteins S100A8 and S100A9 as Novel Diagnostic Markers in Human Prostate Cancer

S-Nitrosylated S100A8: Novel Anti-Inflammatory Properties

Calprotectin (S100A8/S100A9), an Inflammatory Protein Complex from Neutrophils with a Broad Apoptosis-Inducing Activity

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