Heparin is an adhesive ligand for the leukocyte integrin Mac-1 (CD11b/CD1).

Diamond, Michael S.; Alon, Ronen; Parkos, Charles A.; Quinn, Mark T.; Springer, Timothy A.

doi:10.1083/jcb.130.6.1473

Cited by 261 publications

(209 citation statements)

References 73 publications

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“…Mac-1 (CD11b/CD18), a monocytic counter-receptor for ICAM-1 that also binds to heparin (12), is present on Mono Mac 6 but not U937 cells, and may thus explain these differences in adhesion (11). Consistently, oxLDL induces a two-fold upregulation of ICAM-1 but not vas-cular cell adhesion molecule (VCAM)-1 or E-selectin surface expression on HUVEC.…”

Section: Monocyte Adhesion To Oxidized Low Density Lipoprotein-stimulmentioning

confidence: 91%

“…Distinct endothelial ligands induced by mmLDL (8, 9) do not appear to be identical with such ligands (16), since they mediate U937 adhesion, which is not increased by oxLDL. An inhibition of monocyte adhesion with the soluble Mac-1 ligand heparin (12) indicates that cellular heparan sulfate proteoglycans are involved in monocyte adhesion to untreated HUVEC. While heparin alone has no effect, combining heparin with ICAM-1 mAbs significantly inhibits monocyte adhesion to oxLDL-stimulated HUVEC.…”

Section: Monocyte Adhesion To Oxidized Low Density Lipoprotein-stimulmentioning

confidence: 99%

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Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Weber¹,

Erl²,

Weber³

et al. 1999

CCLM

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The integrin heterodimer CD11b/CD18 (␣M␤2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2␣ (8-epi-PGF2␣) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear-resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet ␣IIb␤3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac-1-mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro, indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs.

show abstract

Section: Monocyte Adhesion To Oxidized Low Density Lipoprotein-stimulmentioning

confidence: 91%

Section: Monocyte Adhesion To Oxidized Low Density Lipoprotein-stimulmentioning

confidence: 99%

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Weber¹,

Erl²,

Weber³

et al. 1999

CCLM

View full text Add to dashboard Cite

show abstract

“…Mac-1 has also been shown to bind directly to heparan sulphate [130]. Assays carried out under conditions of physiological flow showed that Mac-1-heparan sulphate binding is not sufficient to mediate neutrophil adhesion.…”

Section: Cell-cell Adhesionmentioning

confidence: 99%

“…Neutrophil binding to E-selectin-coated surfaces causes reversible tethering (rolling), but is not able to support firm adhesion (arrest) at physiological shear stresses. When E-selectin and heparan sulphate are co-adsorbed on to a substratum, both receptors are utilized, so that E-selectin-mediated rolling allows the binding of Mac-1 to heparan sulphate to occur, resulting in firm adhesion of neutrophils at physiological shear stresses [130].…”

Section: Cell-cell Adhesionmentioning

confidence: 99%

Syndecans: multifunctional cell-surface co-receptors

Carey

1997

Biochemical Journal

621

497

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This review will summarize our current state of knowledge of the structure, biochemical properties and functions of syndecans, a family of transmembrane heparan sulphate proteoglycans. Syndecans bind a variety of extracellular ligands via their covalently attached heparan sulphate chains. Syndecans have been proposed to play a role in a variety of cellular functions, including cell proliferation and cell–matrix and cell–cell adhesion. Syndecan expression is highly regulated and is cell-type- and developmental-stage-specific. The main function of syndecans appears to be to modulate the ligand-dependent activation of primary signalling receptors at the cell surface. Principal functions of the syndecan core proteins are to target the heparan sulphate chains to the appropriate plasma-membrane compartment and to interact with components of the actin-based cytoskeleton. Several functions of the syndecans, including syndecan oligomerization and actin cytoskeleton association, have been localized to specific structural domains of syndecan core proteins.

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“…More than 30 protein and nonprotein molecules have been reported to bind this receptor (22). These ligands include ICAMs 1, 2, and 3 (23), fibrinogen (24), factor X (25), complement C3 fragment (26), urokinase plasminogen activator receptor (27), E-selectin (28), catalase, transferrin (29), and some nonprotein ligands such as LPS (30) and heparin (31), etc.…”

mentioning

confidence: 99%

The Calcineurin B Subunit (CnB) Is a New Ligand of Integrin αM That Mediates CnB-Induced Apo2L/TRAIL Expression in Macrophages

Liu

Xin

et al. 2012

The Journal of Immunology

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We showed previously that the calcineurin B subunit (CnB) plays an important role in activation of peritoneal macrophage, but the underlying mechanism remained unknown. To examine whether there is a CnB receptor on peritoneal macrophages, we performed the radioligand binding assay of receptors. The receptor saturation binding curve demonstrated high-affinity and specific binding; the maximum binding was 1090 fmol/105 cells, and the Kd was 70.59 pM. Then, we used a CnB affinity resin to trap potential receptors from highly purified peritoneal macrophage membranes. Mass spectrometry analysis showed that the binding protein was mouse integrin αM. We next performed a competition binding experiment to confirm the binding of CnB to integrin αM. This showed that FITC-CnB bound specifically to peritoneal macrophages and that binding was blocked by the addition of integrin αM Ab. We observed that CnB could induce TRAIL gene expression in peritoneal macrophages in vitro and in vivo. Integrin αM Ab blocking, RNA interference, and ligand competition experiments demonstrated that CnB-induced TRAIL expression is dependent on integrin αM. Furthermore, the tumoricidal activity of CnB-activated peritoneal macrophages is partially dependent on TRAIL. In addition, CnB treatment significantly prolongs the survival of mice bearing H22 ascites tumors, which has a positive correlation with the induction level of TRAIL. These results reveal a novel function of the CnB in innate immunity and cancer surveillance. They also point to a new signaling pathway leading to induction of TRAIL and suggest a possible application of CnB in cancer therapy.

show abstract

Heparin is an adhesive ligand for the leukocyte integrin Mac-1 (CD11b/CD1).

Cited by 261 publications

References 73 publications

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Effects of Oxidized Low Density Lipoprotein, Lipid Mediators and Statins on Vascular Cell Interactions

Syndecans: multifunctional cell-surface co-receptors

The Calcineurin B Subunit (CnB) Is a New Ligand of Integrin αM That Mediates CnB-Induced Apo2L/TRAIL Expression in Macrophages

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