A Novel Anionic Modification of <i>N</i>-Glycans on Mammalian Endothelial Cells Is Recognized by Activated Neutrophils and Modulates Acute Inflammatory Responses

Srikrishna, Geetha; Toomre, Derek; Manzi, Adriana E.; Panneerselvam, K.; Freeze, Hudson H.; Varki, Ajit; Varki, Nissi

doi:10.4049/jimmunol.166.1.624

Cited by 32 publications

(61 citation statements)

References 22 publications

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“…A second group of receptors which has been described in S100A8 signaling are carboxylated glycans (13). By staining with mAb GB3.1, we showed, for the first time, carboxylated glycans on chondrocytes.…”

Section: Discussionmentioning

confidence: 82%

“…Complex formation with S100A9 antagonizes these effects, indicating a regulatory role of conformational changes of these 2 proteins on biologic functions (10,11). In addition, S100A8/A9 has been described to interact with endothelial cells, resulting in an inflammatory, thrombotic, and apoptotic phenotype (12)(13)(14)(15). S100A8 is released by macrophages and neutrophils in high amounts during inflammatory arthritis and due to its small size can easily penetrate into the cartilage matrix (16) and bind to chondrocytes.…”

mentioning

confidence: 99%

“…Although TLR-4 is the dominant receptor mediating S100A8 signaling in macrophages (10), other putative binding sites for S100A8/A9 have been suggested, including heparan sulfate, carboxylated N-glycans, and receptor for advanced glycation end products (RAGE) (12,13).…”

mentioning

confidence: 99%

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Stimulation of chondrocyte‐mediated cartilage destruction by S100A8 in experimental murine arthritis

Lent¹,

Grevers²,

Blom³

et al. 2008

Arthritis & Rheumatism

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Objective. To investigate whether S100A8 is actively involved in matrix metalloproteinase (MMP)-mediated chondrocyte activation.Methods. S100A8 and S100A9 proteins were detected in inflamed knee joints from mice with various forms of murine arthritis, using immunolocalization. Murine chondrocyte cell line H4 was stimulated with proinflammatory cytokines or recombinant S100A8. Messenger RNA (mRNA) and protein levels were measured using reverse transcriptase-polymerase chain reaction and intracellular fluorescence-activated cell sorting (FACS). Breakdown of aggrecan on the pericellular surface of the chondrocytes was measured using VDIPEN and NITEGE antibodies and FACS, and breakdown in patellar cartilage was measured by immunolocalization.Results. S100A8 and S100A9 proteins were abundantly expressed in and around chondrocytes in inflamed knee joints after induction of antigen-induced arthritis or onset of spontaneous arthritis in interleukin-1 (IL-1) receptor antagonist-knockout mice. Stimulation of chondrocytes by the proinflammatory cytokines tumor necrosis factor ␣, IL-1␤, IL-17, and interferon-␥ caused strong up-regulation of S100A8 mRNA and protein levels and up-regulation to a lesser extent of S100A9 levels. Stimulation of chondrocytes with S100A8 induced significant up-regulation of MMP-2, MMP-3, MMP-9, MMP-13, ADAMTS-4, and ADAMTS-5 mRNA levels (up-regulated 4, 4, 3, 16, 8, and 4 times, respectively). VDIPEN and NITEGE neoepitopes were significantly elevated in a concentrationdependent manner in chondrocytes treated with 0.2, 1, or 5 g/ml of S100A8. (VDIPEN levels were elevated 17%, 67%, and 108%, respectively, and NITEGE levels were elevated 8%, 33%, and 67%, respectively.) S100A8 significantly increased the effect of IL-1␤ on MMP-3, MMP-13, and ADAMTS-5. Mouse patellae incubated with both IL-1␤ and S100A8 had elevated levels of NITEGE within the cartilage matrix when compared with patellae incubated with IL-1␤ or S100A8 alone.Conclusion. These findings indicate that S100A8 and S100A9 are found in and around chondrocytes in experimental arthritis. S100A8 up-regulates and activates MMPs and aggrecanase-mediated pericellular matrix degradation.Breakdown of the cartilage matrix is one of the hallmarks of rheumatoid arthritis (RA). Cartilage destruction is predominantly mediated by cytokines, enzymes, and oxygen radicals (1,2). These mediators are released by synovial cells and by chondrocytes. In experimental arthritis, clear pericellular activation of chondrocytes is observed based on expression of large amounts of neoepitopes induced by metalloproteinases, which results in pericellular breakdown of the matrix (3), eventually leading to erosion.

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Section: Discussionmentioning

confidence: 82%

mentioning

confidence: 99%

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Stimulation of chondrocyte‐mediated cartilage destruction by S100A8 in experimental murine arthritis

Lent¹,

Grevers²,

Blom³

et al. 2008

Arthritis & Rheumatism

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“…These glycans interacted with cell surface molecules on activated, but not resting, neutrophils (3). A mAb against this novel modification inhibited extravasation of neutrophils and monocytes in a murine model of peritoneal inflammation (3).…”

Section: Two Proteins Modulating Transendothelial Migration Of Leukocmentioning

confidence: 98%

“…Our previous work on a library of bovine lung oligosaccharides led us to find a novel carboxylated glycan that was constitutively expressed on mammalian endothelial cells (2,3). These glycans interacted with cell surface molecules on activated, but not resting, neutrophils (3).…”

Section: Two Proteins Modulating Transendothelial Migration Of Leukocmentioning

confidence: 99%

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

Srikrishna

Panneerselvam

Westphal

et al. 2001

The Journal of Immunology

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134

162

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We recently showed that a class of novel carboxylated N-glycans was constitutively expressed on endothelial cells. Activated, but not resting, neutrophils expressed binding sites for the novel glycans. We also showed that a mAb against these novel glycans (mAbGB3.1) inhibited leukocyte extravasation in a murine model of peritoneal inflammation. To identify molecules that mediated these interactions, we isolated binding proteins from bovine lung by their differential affinity for carboxylated or neutralized glycans. Two leukocyte calcium-binding proteins that bound in a carboxylate-dependent manner were identified as S100A8 and annexin I. An intact N terminus of annexin I and heteromeric assembly of S100A8 with S100A9 (another member of the S100 family) appeared necessary for this interaction. A mAb to S100A9 blocked neutrophil binding to immobilized carboxylated glycans. Purified human S100A8/A9 complex and recombinant human annexin I showed carboxylate-dependent binding to immobilized bovine lung carboxylated glycans and recognized a subset of mannose-labeled endothelial glycoproteins immunoprecipitated by mAbGB3.1. Saturable binding of S100A8/A9 complex to endothelial cells was also blocked by mAbGB3.1. These results suggest that the carboxylated glycans play important roles in leukocyte trafficking by interacting with proteins known to modulate extravasation.

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Preparation of monodisperse magnetic polystyrene microspheres and its surface chemical modification

Liu

Guan

et al. 2011

J of Applied Polymer Sci

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Monodisperse magnetic polystyrene (PS) microspheres were prepared in the presence of PS seed particles and styrene-based magnetic colloid by the method of magnetic colloid swelling polymerization. The PS seed particles were prepared in advance by soap-free emulsion polymerization. Styrene-based magnetic colloid was used for swelling the PS seed particles in the magnetic colloid swelling polymerization process. After polymerization, functional amino groups were introduced onto the surface of the magnetic PS microspheres by surface Friedel-Crafts acylation reaction. The morphology, size distribution, and magnetic properties of magnetic PS microspheres were characterized with scanning electron microscopy (SEM) and vibrating sample magnetometer (VSM), respectively. SEM showed that the magnetic PS microspheres had an average size of 1078 nm with a narrow size distribution. VSM showed that the magnetic PS microspheres were superparamagnetic, and saturation magnetization was found to be 5.714 emu/g. The concentration of functional amino groups on the surface of magnetic PS microspheres was measured by atomic absorption spectroscopy and UVÀVis spectroscopy, and the concentration of amino groups was found to be 0.168 mmol/g.

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A Novel Anionic Modification of N-Glycans on Mammalian Endothelial Cells Is Recognized by Activated Neutrophils and Modulates Acute Inflammatory Responses

Cited by 32 publications

References 22 publications

Stimulation of chondrocyte‐mediated cartilage destruction by S100A8 in experimental murine arthritis

Stimulation of chondrocyte‐mediated cartilage destruction by S100A8 in experimental murine arthritis

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

Preparation of monodisperse magnetic polystyrene microspheres and its surface chemical modification

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