Cited by 288Proteoglycans and glycosaminoglycans researchCell Adhesion Molecules ResearchCarbohydrate Chemistry and Synthesis

The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.

Heparin’s anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectins

Open access

Wang, Lianchun, Brown, Jillian R., Varki, Ajit, Esko, Jeffrey D.·2002·Journal of Clinical Investigation

DOI 10.1172/jci0214996

Open this paper in CoChat — free account Open PDF

Abstract

Heparin has been used clinically as an anticoagulant and antithrombotic agent for over 60 years.Here we show that the potent anti-inflammatory property of heparin results primarily from blockade of P-selectin and L-selectin.Unfractionated heparin and chemically modified analogs were tested as inhibitors of selectin binding to immobilized sialyl Lewis X and of cell adhesion to immobilized selectins or thrombin-activated endothelial cells.Compared with unfractionated heparin, the modified heparinoids had inhibitory activity in this general order: over-O-sulfated heparin > heparin > 2-O,3-O-desulfated ≥ N-desulfated/N-acetylated heparin ≥ carboxyl-reduced heparin ≥ N-,2-O,3-Odesulfated heparin >> 6-O-desulfated heparin.The heparinoids also showed similar differences in their ability to inhibit thioglycollate-induced peritonitis and oxazolone-induced delayed-type hypersensitivity.Mice deficient in P-or L-selectins showed impaired inflammation, which could be further reduced by heparin.However, heparin had no additional effect in mice deficient in both P-and L-selectins.We conclude that (a) heparin's anti-inflammatory effects are mainly mediated by blocking P-and L-selectin-initiated cell adhesion; (b) the sulfate groups at C6 on the glucosamine residues play a critical role in selectin inhibition; and (c) some non-anticoagulant forms of heparin retain anti-inflammatory activity.Such analogs may prove useful as therapeutically effective inhibitors of inflammation.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1172/jci0214996

Cites

72 of 72 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm
Springer, T. A. (1994) · Cell · doi:10.1016/0092-8674(94)90337-9 · Cited by 7,009
Lymphocyte Homing and Homeostasis
Butcher, E. C., & Picker, L. J. (1996) · Science · doi:10.1126/science.272.5258.60 · Cited by 2,846
Selectins and their ligands: Current concepts and controversies
Kansas, G. (1996) · Blood · doi:10.1182/blood.v88.9.3259.bloodjournal8893259 · Cited by 1,415
Molecular diversity of heparan sulfate
Esko, J. D., & Lindahl, U. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200113530 · Cited by 978
Self-citation
Selectin ligands.
Varki, A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.16.7390 · Cited by 946
Self-citation
Mechanisms That Regulate the Function of the Selectins and Their Ligands
VESTWEBER, D., & BLANKS, J. E. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.1.181 · Cited by 932
Formation of anhydrosugars in the chemical depolymerization of heparin
Shively, J. E., & Conrad, H. E. (1976) · Biochemistry · doi:10.1021/bi00663a005 · Cited by 905
The α(1,3)Fucosyltransferase Fuc-TVII Controls Leukocyte Trafficking through an Essential Role in L-, E-, and P-selectin Ligand Biosynthesis
Malý, P., Thall, A. D., Petryniak, B., Rogers, C. E., Smith, P. L., Marks, R. M., Kelly, R. J., Gersten, K. M., Cheng, G., Saunders, T. L., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80137-3 · Cited by 714
Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis
Borsig, L., Wong, R., Feramisco, J., Nadeau, D. R., Varki, N. M., & Varki, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061615598 · Cited by 714
Self-citation
Glycosaminoglycans Interact Selectively with Chemokines and Modulate Receptor Binding and Cellular Responses
Kuschert, G. S. V., Coulin, F., Power, C. A., Proudfoot, A. E. I., Hubbard, R. E., Hoogewerf, A. J., & Wells, T. N. C. (1999) · Biochemistry · doi:10.1021/bi990711d · Cited by 575

Show all 72 references

Research works printed but not linked: 5

Ramos, 1998, Blood, 91, 1067, 10.1182/blood.V91.3.1067 · DOI
Takada, 1993, Cancer Res, 53, 354
Lefer, 1996, Am J Physiol, 270, H88
Ley, 1991, Am J Physiol, 260, 1667
Catalina, 1999, Blood, 93, 580, 10.1182/blood.V93.2.580 · DOI

Sorted by citations

Heparin prevents antiphospholipid antibody–induced fetal loss by inhibiting complement activation
Girardi, G., Redecha, P. B., & Salmon, J. E. (2004) · Nature Medicine · doi:10.1038/nm1121 · Cited by 680
The role of heparan sulphate in inflammation
Parish, C. R. (2006) · Nature reviews. Immunology · doi:10.1038/nri1918 · Cited by 513
Endothelial heparan sulfate deficiency impairs L-selectin- and chemokine-mediated neutrophil trafficking during inflammatory responses
Wang, L., Fuster, M., Sriramarao, P., & Esko, J. D. (2005) · Nature Immunology · doi:10.1038/ni1233 · Cited by 413
Self-citation
L-selectin: A Major Regulator of Leukocyte Adhesion, Migration and Signaling
Ívetic, A., Green, H. L. H., & Hart, S. J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01068 · Cited by 493
The anti-inflammatory effects of heparin and related compounds
Young, E. (2007) · Thrombosis Research · doi:10.1016/j.thromres.2006.10.026 · Cited by 397
Endothelial Cell Glycocalyx Modulates Immobilization of Leukocytes at the Endothelial Surface
Constantinescu, A. A., Vink, H., & Spaan, J. A. E. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000085630.24353.3d · Cited by 380
Inhibition of Toll-Like Receptor Signaling as a Promising Therapy for Inflammatory Diseases: A Journey from Molecular to Nano Therapeutics
Gao, W., Xiong, Y., Li, Q., & Yang, H. Y. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00508 · Cited by 372
Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas
Wahrenbrock, M., Borsig, L., Le, D., Varki, N., & Varki, A. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200318882 · Cited by 317
Self-citation
Heparan Sulfate: Biosynthesis, Structure, and Function
Li, J.-P., & Kusche‐Gullberg, M. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.02.009 · Cited by 312
Heparin: Past, Present, and Future
Oduah, E., Linhardt, R. J., & Sharfstein, S. T. (2016) · Pharmaceuticals · doi:10.3390/ph9030038 · Cited by 282
Chapter 3 Interactions Between Heparan Sulfate and Proteins—Design and Functional Implications
Lindahl, U., & Li, J. (2009) · International review of cytology · doi:10.1016/s1937-6448(09)76003-4 · Cited by 288
Dendritic polyglycerol sulfates as multivalent inhibitors of inflammation
Dernedde, J., Rausch, A., Weinhart, M., Enders, S., Tauber, R., Licha, K., Schirner, M., Zügel, U., von Bonin, A., & Haag, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003103107 · Cited by 276
Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis
Guglietta, S., Chiavelli, A., Zagato, E., Krieg, C., Gandini, S., Ravenda, P. S., Bazolli, B., Lu, B., Penna, G., & Rescigno, M. (2016) · Nature Communications · doi:10.1038/ncomms11037 · Cited by 260
HSulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes heparin-bound growth factors and chemokines: effects on VEGF, FGF-1, and SDF-1
Uchimura, K., Morimoto‐Tomita, M., Bistrup, A., Li, J., Lyon, M., Gallagher, J. T., Werb, Z., & Rosen, S. D. (2006) · BMC Biochemistry · doi:10.1186/1471-2091-7-2 · Cited by 236
Differential Metastasis Inhibition by Clinically Relevant Levels of Heparins—Correlation with Selectin Inhibition, Not Antithrombotic Activity
Stevenson, J. L., Choi, S. H., & Varki, A. P. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1131 · Cited by 219
Self-citation
A National and Single Institutional Experience in the Contemporary Treatment of Acute Lower Extremity Ischemia
Eliason, J. L., Wainess, R. M., Proctor, M., Dimick, J. B., Cowan, J. A., Upchurch, G. R., Stanley, J. C., & Henke, P. K. (2003) · Annals of Surgery · doi:10.1097/01.sla.0000086663.49670.d1 · Cited by 207
More than an anticoagulant: Do heparins have direct anti-inflammatory effects?
Poterucha, T. J., Libby, P., & Goldhaber, S. Z. (2016) · Thrombosis and Haemostasis · doi:10.1160/th16-08-0620 · Cited by 198
Endothelial P-Selectin as a Target of Heparin Action in Experimental Melanoma Lung Metastasis
Ludwig, R. J., Boehme, B., Podda, M., Henschler, R., Jäger, E., Tandi, C., Boehncke, W., Zollner, T. M., Kaufmann, R., & Gille, J. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-1054 · Cited by 195
Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects
Fedorov, S., Ermakova, S., Zvyagintseva, T., & Stonik, V. (2013) · Marine Drugs · doi:10.3390/md11124876 · Cited by 189
Clinical review: Anticoagulation for continuous renal replacement therapy - heparin or citrate?
Straaten, H. M. O., Kellum, J. A., & Bellomo, R. (2010) · Critical Care · doi:10.1186/cc9358 · Cited by 190
Selectin Blocking Activity of a Fucosylated Chondroitin Sulfate Glycosaminoglycan from Sea Cucumber
Borsig, L., Wang, L., Cavalcante, M. C. M., Cardilo-Reis, L., Ferreira, P. L., Mourąo, P. A. S., Esko, J. D., & Pavąo, M. S. G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610560200 · Cited by 187
Self-citation
Cancer and thrombosis: from molecular mechanisms to clinical presentations
Buller, H. R., van Doormaal, F. F., Sluis, G. L. V., & Kamphuisen, P. W. (2007) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2007.02497.x · Cited by 177
Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine
Gerotziafas, G., Catalano, M., Colgan, M. P., Pécsvárady, Z., Wautrecht, J. C., Fazeli, B., Olinic, D.-M., Farkas, K., Elalamy, I., Falanga, A., et al. (2020) · Thrombosis and Haemostasis · doi:10.1055/s-0040-1715798 · Cited by 171
Recurrent pregnancy loss: A disease of inflammation and coagulation
Kwak-Kim, J. Y.-H., Yang, K. M., & Gilman‐Sachs, A. (2009) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2009.01079.x · Cited by 171
Role of the coagulation system in acetaminophen-induced hepatotoxicity in mice
Ganey, P. E., Luyendyk, J. P., Newport, S. W., Eagle, T. M., Maddox, J. F., Mackman, N., & Roth, R. A. (2007) · Hepatology · doi:10.1002/hep.21779 · Cited by 165
Syndecan-1 shedding facilitates the resolution of neutrophilic inflammation by removing sequestered CXC chemokines
Hayashida, K., Parks, W. C., & Park, P. W. (2009) · Blood · doi:10.1182/blood-2009-02-204966 · Cited by 163
The glycocalyx: a central regulator of vascular function
Moore, K. H., Murphy, H. A., & George, E. M. (2021) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00340.2020 · Cited by 159
Therapeutic Intervention and Targets for Sepsis
Rice, T. W., & Bernard, G. R. (2004) · Annual Review of Medicine · doi:10.1146/annurev.med.56.082103.104356 · Cited by 159
Tissue factor mediates inflammation
Chu, A. J. (2005) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2005.06.005 · Cited by 156
A Novel Biological Activity for Galectin-1
La, M., Cao, T. V., Cerchiaro, G., Chilton, K., Hirabayashi, J., Kasai, K., Oliani, S. M., Chernajovsky, Y., & Perretti, M. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63507-9 · Cited by 149
Low anticoagulant heparin targets multiple sites of inflammation, suppresses heparin-induced thrombocytopenia, and inhibits interaction of RAGE with its ligands
Rao, N. V., Argyle, B., Xu, X., Reynolds, P. R., Walenga, J. M., Prechel, M., Prestwich, G. D., MacArthur, R. B., Walters, B. B., Hoidal, J. R., et al. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00009.2010 · Cited by 144
Heparanase: roles in cell survival, extracellular matrix remodelling and the development of kidney disease
Rabelink, T. J., van den Berg, B. M., Garsen, M., Wang, G., Elkin, M., & van der Vlag, J. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.6 · Cited by 138
Venous thromboembolism in malignant gliomas
Jenkins, E., Schiff, D., Mackman, N., & Key, N. S. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03690.x · Cited by 136
Bioengineered heparins and heparan sulfates
Fu, L., Suflita, M., & Linhardt, R. J. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.11.002 · Cited by 138
P‐selectin‐ and heparanase‐dependent antimetastatic activity of non‐anticoagulant heparins
Hostettler, N., Naggi, A., Torri, G., Ishai-Michaeli, R., Casu, B., Vlodavsky, I., & Borsig, L. (2007) · The FASEB Journal · doi:10.1096/fj.07-8450com · Cited by 132
Heparan sulfate as a regulator of inflammation and immunity
Collins, L. E., & Troeberg, L. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ru0618-246r · Cited by 130
Heparan sulfate proteoglycans in glomerular inflammation
Rops, A. L. W. M. M., van der Vlag, J., Lensen, J. F. M., Wijnhoven, T. J. M., van den Heuvel, L. P. W. J., Kuppevelt, T. H. V., & Berden, J. H. M. (2004) · Kidney International · doi:10.1111/j.1523-1755.2004.00451.x · Cited by 131
Role of the endothelial surface layer in neutrophil recruitment
Márki, A., Esko, J. D., Pries, A. R., & Ley, K. F. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.3mr0115-011r · Cited by 128
Self-citation
Sulfated glycans in inflammation
Pomin, V. H. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.01.002 · Cited by 124
Proteoglycans: Key Regulators of Pulmonary Inflammation and the Innate Immune Response to Lung Infection
Gill, S. E., Wight, T. N., & Frevert, C. W. (2010) · The Anatomical Record · doi:10.1002/ar.21094 · Cited by 123
Activated, Not Resting, Platelets Increase Leukocyte Rolling in Murine Skin Utilizing a Distinct Set of Adhesion Molecules
Ludwig, R. J., Schultz, J. E., Boehncke, W., Podda, M., Tandi, C., Krombach, F., Baatz, H., Kaufmann, R., von Andrian, U. H., & Zollner, T. M. (2004) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2004.22318.x · Cited by 120
Contribution of Proteoglycans to Human Immunodeficiency Virus Type 1 Brain Invasion
Bobardt, M. D., Salmon, P., Wang, L., Esko, J. D., Gabuzda, D. H., Fiala, M., Trono, D., der Schueren, B. V., David, G., & Gallay, P. A. (2004) · Journal of Virology · doi:10.1128/jvi.78.12.6567-6584.2004 · Cited by 120
Self-citation
Tunable Heparan Sulfate Mimetics for Modulating Chemokine Activity
Sheng, G. J., Oh, Y. I., Chang, S., & Hsieh‐Wilson, L. C. (2013) · Journal of the American Chemical Society · doi:10.1021/ja4027727 · Cited by 121
Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies
Krauel, K., Hackbarth, C., Fürll, B., & Greinacher, A. (2011) · Blood · doi:10.1182/blood-2011-05-353391 · Cited by 116
Low molecular weight heparins prevent the induction of autophagy of activated neutrophils and the formation of neutrophil extracellular traps
Manfredi, A. A., Rovere, P. Q., D’Angelo, A., & Maugeri, N. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2016.08.008 · Cited by 114
Endogenous Attenuation of Allergic Lung Inflammation by Syndecan-1
Xu, J., Park, P. W., Kheradmand, F., & Corry, D. B. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.9.5758 · Cited by 99
Inactivation of heparan sulfate 2-O-sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice
Axelsson, J. B., Xu, D., Kang, B. N., Nussbacher, J. K., Handel, T. M., Ley, K. F., Sriramarao, P., & Esko, J. D. (2012) · Blood · doi:10.1182/blood-2012-03-417139 · Cited by 101
Self-citation
The Role of Heparan Sulfate in Inflammation, and the Development of Biomimetics as Anti-Inflammatory Strategies
Farrugia, B. L., Lord, M. S., Melrose, J., & Whitelock, J. M. (2018) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155417740881 · Cited by 100
Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review
Tvaroška, I., Selvaraj, C., & Koča, J. (2020) · Molecules · doi:10.3390/molecules25122835 · Cited by 98
The “in and out” of glucosamine 6-O-sulfation: the 6th sense of heparan sulfate
Masri, R. E., Seffouh, A., Lortat‐Jacob, H., & Vivès, R. R. (2016) · Glycoconjugate Journal · doi:10.1007/s10719-016-9736-5 · Cited by 92
Glycan Antagonists and Inhibitors: A Fount for Drug Discovery
Brown, J. R., Crawford, B. E., & Esko, J. D. (2007) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409230701751611 · Cited by 88
Self-citation
Sulfated galactofucan from Lobophora variegata: Anticoagulant and anti-inflammatory properties
Medeiros, V. P., Queiroz, K. C. S., Cardoso, M. L., Monteiro, G. R., Oliveira, F. W., Chavante, S. F., Guimaraes, L. A., Rocha, H. A. O., & Leite, E. L. (2008) · Biochemistry (Moscow) · doi:10.1134/s0006297908090095 · Cited by 86
A Highly Conserved Arginine in gp120 Governs HIV-1 Binding to Both Syndecans and CCR5 via Sulfated Motifs
de Parseval, A., Bobardt, M. D., Chatterji, A., Chatterji, U., Elder, J. H., David, G., Zolla‐Pazner, S., Farzan, M., Lee, T., & Gallay, P. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504233200 · Cited by 84
A mutant-cell library for systematic analysis of heparan sulfate structure–function relationships
Qiu, H. Y., Shi, S., Yue, J., Xin, M., Nairn, A. V., Lin, L., Liu, X., Li, G., Archer‐Hartmann, S. A., Rosa, M. D., et al. (2018) · Nature Methods · doi:10.1038/s41592-018-0189-6 · Cited by 82
Self-citation
Ascidian dermatan sulfates attenuate metastasis, inflammation and thrombosis by inhibition of P‐selectin
Kozlowski, E. O., Pavão, M. S. G., & Borsig, L. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04401.x · Cited by 80
Enoxaparin Improves the Course of Dextran Sodium Sulfate-Induced Colitis in Syndecan-1-Deficient Mice
Floer, M., Götte, M., Wild, M. K., Heidemann, J., Gassar, E. S., Domschke, W., Kiesel, L., Luegering, A., & Kucharzik, T. F. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2010.080639 · Cited by 85
Treatment with an oral small molecule inhibitor of P selectin (PSI-697) decreases vein wall injury in a rat stenosis model of venous thrombosis
Myers, D. D., Henke, P. K., Bedard, P. W., Wrobleski, S. K., Kaila, N., Shaw, G. D., Meier, T. R., Hawley, A. E., Schaub, R. G., & Wakefield, T. W. (2006) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2006.05.021 · Cited by 80
Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial
Dixon, B., Smith, R. J., Campbell, D. J., Moran, J. L., Doig, G. S., Rechnitzer, T., MacIsaac, C., Simpson, N., van Haren, F. M. P., Ghosh, A., et al. (2021) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30470-7 · Cited by 81
Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?
Maugeri, N., GIORDANO, G., Petrilli, M. P., Fraticelli, V. L., de Gaetano, G., Cerletti, C., Storti, S., & Donati, M. B. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.02194.x · Cited by 79
Anti-inflammatory properties of a heparin-like glycosaminoglycan with reduced anti-coagulant activity isolated from a marine shrimp
Brito, A. S., Arimatéia, D. S., Souza, L. R., Lima, M. A., Santos, V. O., Medeiros, V. P., Ferreira, P. A., Silva, R. A., Ferreira, C. V., Justo, G. Z., et al. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.09.020 · Cited by 77
The role of low-molecular-weight heparin in recurrent implantation failure: a prospective, quasi-randomized, controlled study
Berker, B., Taşkın, S., Kahraman, K., Taşkın, E. A., Atabekoğlu, C. S., & Sönmezer, M. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.12.033 · Cited by 77
Subendothelial Heparan Sulfate Proteoglycans Become Major L-Selectin and Monocyte Chemoattractant Protein-1 Ligands upon Renal Ischemia/Reperfusion
Celie, J. W. A. M., Rutjes, N. W. P., Keuning, E. D., Soininen, R., Heljäsvaara, R., Pihlajaniemi, T. A., Dräger, A. M., Zweegman, S., Kessler, F. L., Beelen, R. H. J., et al. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.070061 · Cited by 79
The antiphospholipid syndrome as a disorder initiated by inflammation: implications for the therapy of pregnant patients
Salmon, J. E., Girardi, G., & Lockshin, M. D. (2007) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0432 · Cited by 74
The Role of Dimension in Multivalent Binding Events: Structure–Activity Relationship of Dendritic Polyglycerol Sulfate Binding to L ‐Selectin in Correlation with Size and Surface Charge Density
Weinhart, M., Gröger, D., Enders, S., Riese, S. B., Dernedde, J., Kainthan, R. K., Brooks, D. E., & Haag, R. (2011) · Macromolecular Bioscience · doi:10.1002/mabi.201100051 · Cited by 73
Antithrombotics from the Sea: Polysaccharides and Beyond
Carvalhal, F., Cristelo, R. R., Resende, D. I. S. P., Pinto, M. M. M., Sousa, E., & Correia‐da‐Silva, M. (2019) · Marine Drugs · doi:10.3390/md17030170 · Cited by 76
Novel Sulfated Polysaccharides Disrupt Cathelicidins, Inhibit RAGE and Reduce Cutaneous Inflammation in a Mouse Model of Rosacea
Zhang, J., Xu, X., Rao, N. V., Argyle, B., McCoard, L., Rusho, W. J., Kennedy, T. P., Prestwich, G. D., & Krueger, G. G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016658 · Cited by 73
Sulfated Alginates as Heparin Analogues: A Review of Chemical and Functional Properties
Arlov, Ø., & Skjåk‐Bræk, G. (2017) · Molecules · doi:10.3390/molecules22050778 · Cited by 75
Heparin Reduces Neuroinflammation and Transsynaptic Neuronal Apoptosis in a Model of Subarachnoid Hemorrhage
Simard, J. M., Tosun, Ç., Ivanova, S., Kurland, D. B., Hong, C. M., Radecki, L., Gisriel, C., Mehta, R. I., Schreibman, D. L., & Gerzanich, V. (2012) · Translational Stroke Research · doi:10.1007/s12975-012-0166-9 · Cited by 72
Modified Heparin Inhibits P-selectin-mediated Cell Adhesion of Human Colon Carcinoma Cells to Immobilized Platelets under Dynamic Flow Conditions
Wei, M., Tai, G., Gao, Y., Li, N., Huang, B., Zhou, Y., Hao, S., & Zeng, X. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312951200 · Cited by 72
Core 2 Branching β1,6-N-Acetylglucosaminyltransferase and High Endothelial Venule-restricted Sulfotransferase Collaboratively Control Lymphocyte Homing
Hiraoka, N., Kawashima, H., Petryniak, B., Nakayama, J., Mitoma, J., Marth, J. D., Lowe, J. B., & Fukuda, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311150200 · Cited by 70
Programmable one-pot synthesis of heparin pentasaccharides enabling access to regiodefined sulfate derivatives
Dey, S., & Wong, C. (2018) · Chemical Science · doi:10.1039/c8sc01743c · Cited by 68
Oral heparin: status review.
Arbit, E., Goldberg, M. F., Gómez-Orellana, I., & Majuru, S. (2006) · Thrombosis Journal · doi:10.1186/1477-9560-4-6 · Cited by 68
Combinatorial one-pot chemoenzymatic synthesis of heparin
Bhaskar, U., Li, G., Fu, L., Onishi, A., Suflita, M., Dordick, J. S., & Linhardt, R. J. (2014) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2014.10.054 · Cited by 68
Pathogenic role of anti-β2-glycoprotein I antibodies on human placenta: functional effects related to implantation and roles of heparin
Simone, N. D., Meroni, P. L., D’Asta, M., Nicuolo, F. D., D’Alessio, M. C., & Caruso, A. (2006) · Human Reproduction Update · doi:10.1093/humupd/dml051 · Cited by 67
Characterization and Quantification of Highly Sulfated Glycosaminoglycan Isomers by Gated-Trapped Ion Mobility Spectrometry Negative Electron Transfer Dissociation MS/MS
Wei, J., Wu, J., Tang, Y., Ridgeway, M. E., Park, M. A., Costello, C. E., Zaia, J., & Lin, C. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b05283 · Cited by 68
Heparan sulfate domains on cultured activated glomerular endothelial cells mediate leukocyte trafficking
Rops, A. L. W. M. M., van den Hoven, M. J., Baselmans, M. M., Lensen, J. F. M., Wijnhoven, T. J. M., van den Heuvel, L. P., Kuppevelt, T. H. V., Berden, J. H. M., & van der Vlag, J. (2007) · Kidney International · doi:10.1038/sj.ki.5002573 · Cited by 67
Immunologic insights in recurrent spontaneous abortion: Molecular mechanisms and therapeutic interventions
Guan, D., Sun, W., Gao, M., Chen, Z., & Ma, X. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117082 · Cited by 65
Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity
Lanzi, C., & Cassinelli, G. (2018) · Molecules · doi:10.3390/molecules23112915 · Cited by 66
State‐of‐the‐art glycosaminoglycan characterization
Zappe, A., Miller, R. L., Struwe, W. B., & Pagel, K. (2021) · Mass Spectrometry Reviews · doi:10.1002/mas.21737 · Cited by 63
Sulfated polysaccharides identified as inducers of neuropilin-1 internalization and functional inhibition of VEGF165 and semaphorin3A
Narazaki, M., Segarra, M., & Tosato, G. (2008) · Blood · doi:10.1182/blood-2007-09-112474 · Cited by 59
Glycosaminoglycans analogs from marine invertebrates: structure, biological effects, and potential as new therapeutics
Pavão, M. S. G. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00123 · Cited by 60
Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis
Bloom, S. L., Kiilerich, S., Lassen, M. R., Forbes, A., Leiper, K., Langholz, E., Irvine, E. J., O'Morain, C. A., Lowson, D., & Orm, S. A. (2004) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2004.01926.x · Cited by 60
Unfractionated heparin and new heparin analogues from ascidians (chordate-tunicate) ameliorate colitis in rats
Belmiro, C. L. R., Castelo-Branco, M. T. L., Melim, L. M. C., Schanaider, A., Elia, C., Madi, K., Pavão, M. S. G., & de Souza, H. S. P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807211200 · Cited by 57
Remodeling articular immune homeostasis with an efferocytosis-informed nanoimitator mitigates rheumatoid arthritis in mice
Zhang, S., Liu, Y., Jing, W., Chai, Q., Tang, C., Li, Z., Man, Z., Chen, C., Zhang, J., Sun, P., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36468-2 · Cited by 57
An in vitro evaluation of inflammation response of titanium functionalized with heparin/fibronectin complex
Li, G., Yang, P., Guo, X., Huang, N., & Shen, R. (2011) · Cytokine · doi:10.1016/j.cyto.2011.06.020 · Cited by 59
Quantitative description of thermodynamic and kinetic properties of the platelet factor 4/heparin bonds
Nguyen, T., Greinacher, A., & Delcea, M. (2015) · Nanoscale · doi:10.1039/c5nr02132d · Cited by 57
Heparin for assisted reproduction
Akhtar, M. A., Sur, S. D., Raine‐Fenning, N., Jayaprakasan, K., Thornton, J., & Quenby, S. M. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009452.pub2 · Cited by 57
Heparan sulfate and inflammation
Parish, C. R. (2005) · Nature Immunology · doi:10.1038/ni0905-861 · Cited by 57
Modulation of heparan sulfate in the glomerular endothelial glycocalyx decreases leukocyte influx during experimental glomerulonephritis
Rops, A. L. W. M. M., Loeven, M. A., van Gemst, J. J., Eversen, I., van Wijk, X. M., Dijkman, H. B. P. M., Kuppevelt, T. H. V., Berden, J. H. M., Rabelink, T. J., Esko, J. D., et al. (2014) · Kidney International · doi:10.1038/ki.2014.115 · Cited by 58
Self-citation
Proteoglycans as Immunomodulators of the Innate Immune Response to Lung Infection
Kang, I., Chang, M. Y., Wight, T. N., & Frevert, C. W. (2018) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155417751880 · Cited by 53
Heparan Sulfate Facilitates Spike Protein-Mediated SARS-CoV-2 Host Cell Invasion and Contributes to Increased Infection of SARS-CoV-2 G614 Mutant and in Lung Cancer
Yue, J., Jin, W., Yang, H., Faulkner, J., Song, X., Qiu, H. Y., Teng, M. N., Azadi, P., Zhang, F., Linhardt, R. J., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.649575 · Cited by 53
Self-citation
Heparin: an intervenor in cell communication
Xu, X., & Dai, Y. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00871.x · Cited by 55
Management of Women with Recurrent Pregnancy Losses and Antiphospholipid Antibody Syndrome
Kwak-Kim, J. Y.-H., Jesus, M. S. L. A., Alentajan-Aleta, L. T., Liao, A., Ota, K., Dambaeva, S. V., Beaman, K. D., Kim, J. W., & Gilman‐Sachs, A. (2013) · American Journal of Reproductive Immunology · doi:10.1111/aji.12114 · Cited by 52
A Disaccharide-Based Inhibitor of Glycosylation Attenuates Metastatic Tumor Cell Dissemination
Brown, J. R., Fuster, M. M., Li, R., Varki, N. M., Glass, C. A., & Esko, J. D. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2745 · Cited by 53
Self-citation
The influence of various structural parameters of semisynthetic sulfated polysaccharides on the P-selectin inhibitory capacity
Fritzsche, J., Alban, S., Ludwig, R. J., Rubant, S., Boehncke, W., Schumacher, G., & Bendas, G. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.05.006 · Cited by 52
Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell‐induced vaso‐occlusion
Telen, M. J., Batchvarova, M., Shan, S., Bovée‐Geurts, P. H. M., Zennadi, R., Leitgeb, A. M., Brock, R. E., & Lindgren, M. (2016) · British Journal of Haematology · doi:10.1111/bjh.14303 · Cited by 53
Elucidating the Interactions Between Heparin/Heparan Sulfate and SARS-CoV-2-Related Proteins—An Important Strategy for Developing Novel Therapeutics for the COVID-19 Pandemic
Yu, M., Zhang, T., Zhang, W., Sun, Q., Li, H., & Li, J. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.628551 · Cited by 52
The heparan sulfate proteoglycan grip on hyperlipidemia and atherosclerosis
Gordts, P. L. S. M., & Esko, J. D. (2018) · Matrix Biology · doi:10.1016/j.matbio.2018.05.010 · Cited by 53
Self-citation
The synthetic pentasaccharide fondaparinux reduces coagulation, inflammation and neutrophil accumulation in kidney ischemia–reperfusion injury
Frank, R. D., Schabbauer, G., Holscher, T. D., Sato, Y. Z., Tencati, M., Pawliński, R., & Mackman, N. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01188.x · Cited by 51
Heparosan‐Derived Heparan Sulfate/Heparin‐Like Compounds: One Kind of Potential Therapeutic Agents
Li, P., Sheng, J., Liu, Y., Li, J., Liu, J., & Wang, F. (2012) · Medicinal Research Reviews · doi:10.1002/med.21263 · Cited by 47

Authors: Wang, L., Brown, J. R., Varki, A., & Esko, J. D.
Affiliations: University of California San Diego (US)
Corresponding author: Esko, Jeffrey D.
ORCID: Wang, Lianchun
Brown, Jillian R.
Varki, Ajit
Esko, Jeffrey D.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2002-07-01
Volume: 110
Issue: 1
Pages: 127-136
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci0214996
OpenAlex: W4250801983
Cited by: 288
References: 72
Citations by year: 2026: 9 · 2025: 5 · 2024: 9 · 2023: 6 · 2022: 3 · 2021: 11 · 2020: 11 · 2019: 9 · 2018: 14 · 2017: 11 · 2016: 16 · 2015: 15 · 2014: 11 · 2013: 15 · 2012: 12
FWCI: 5.35
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Funders: National Institutes of Health
University of California, San Diego
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
Keywords: heparin, anti-inflammatory activity, P-selectin, L-selectin, cell adhesion, sialyl Lewis X, heparinoids, peritonitis, delayed-type hypersensitivity, inflammation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Heparin’s anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectins

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks