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. 2013 Mar 7;18(2):200–208. doi: 10.2478/s11658-013-0084-1

Sulfochitosan inhibits P-selectin-mediated HL-60 leukocyte adhesion under flow conditions

Jinfeng Huang 1, Ruifei Wang 1, Ximing Liu 1, Xianlu Zeng 1,✉, Min Wei 1,✉
PMCID: PMC6275797  PMID: 23468382

Abstract

Excessive trafficking of leukocytes can lead to serious tissue injury. Here, four regioselectively sulfated chitosans were assessed as inhibitors of HL-60 leukocyte binding to P-selectin, by investigating their effect on leukocyte adhesion to CHO cells expressing human P-selectin under static and flow conditions. The results show that the sulfochitosans exhibit inhibitory activity in this general order: heparin > N-sulfated/6-O-sulfated chitosan ≥ 3-O,6-O-sulfated chitosan > 6-O-sulfated chitosan ≫ N-sulfated chitosan. This suggests that the sulfation of the double site in chitosan is essential for efficient inhibition of P-selectin-mediated HL-60 leukocyte adhesion and that such sulfochitosans may have potential as therapeutic agents against inflammatory disease.

Key words: Chitosan, Sulfated chitosan, P-selectin, Inhibition, Cell adhesion, Flow condition, Heparin

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Abbreviations used

AC1.2

a non-blocking mAb against P-selectin

DMF

dimethylformamide

FBS

fetal bovine serum

HPLC

high performance liquid chromatography

N-S-C

N-sulfated chitosan

N,6-S-C

N-sulfated/6-O-sulfated chitosan

P-Fc

recombinant human P-selectin/Fc chimera protei

3,6-S-C

3-O,6-Osulfated chitosan

6-S-C

6-O-sulfated chitosan

9E1

a leukocyte adhesion blocking IgG mAb against P-selectin

Contributor Information

Xianlu Zeng, Email: zengx779@nenu.edu.cn.

Min Wei, Email: weim750@nenu.edu.cn.

References

  • 1.Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L. Neutrophils: molecules, functions and pathophysiological aspects. Lab. Invest. 2000;80:617–653. doi: 10.1038/labinvest.3780067. [DOI] [PubMed] [Google Scholar]
  • 2.Albeda SM, Smith CW, Ward PA. Adhesion molecules and inflammatory injury. FASEB J. 1994;8:504–512. [PubMed] [Google Scholar]
  • 3.Lefer AM, Weyrich AS, Buerke M. Role of selectins, a new family of adhesion molecules, in ischaemia-reperfusion injury. Cardiovasc. Res. 1994;28:289–294. doi: 10.1093/cvr/28.3.289. [DOI] [PubMed] [Google Scholar]
  • 4.Rossi B, Constantin G. Anti-selectin therapy for the treatment of inflammatory diseases. Inflamm. Allergy Drug Targets. 2008;7:85–93. doi: 10.2174/187152808785107633. [DOI] [PubMed] [Google Scholar]
  • 5.Etzioni A. Adhesion molecules-Their role in health and disease. Pediatr. Res. 1996;39:191–198. doi: 10.1203/00006450-199602000-00001. [DOI] [PubMed] [Google Scholar]
  • 6.Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell. 1994;76:301–314. doi: 10.1016/0092-8674(94)90337-9. [DOI] [PubMed] [Google Scholar]
  • 7.Sako D, Chang XJ, Barone KM, Vachino G, White HM, Shaw G, Veldman GM, Bean KM, Ahern TJ, Furie B, Cumming DA, Larsen GR. Expression cloning of a functional glycoprotein ligand for P-selectin. Cell. 1993;75:1179–1186. doi: 10.1016/0092-8674(93)90327-m. [DOI] [PubMed] [Google Scholar]
  • 8.McEver RP, Cummings RD. Role of PSGL-1 binding to selectins in leukocyte recruitment. J. Clin. Invest. 1997;100:S97–103. [PubMed] [Google Scholar]
  • 9.Stoolman LM. Adhesion molecules controlling lymphocyte migration. Cell. 1989;56:907–910. doi: 10.1016/0092-8674(89)90620-x. [DOI] [PubMed] [Google Scholar]
  • 10.Varki A. Selectin ligands. Proc. Natl. Acad. Sci. USA. 1994;91:7390–7397. doi: 10.1073/pnas.91.16.7390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Nelson RM, Cecconi O, Roberts WG, Aruffo A, Linhardt RJ, Bevilacqua MP. Heparin oligosaccharides bind L- and P-selectin and inhibit acute inflammation. Blood. 1993;82:3253–3258. [PubMed] [Google Scholar]
  • 12.Wei M, Tai G, Gao Y, Li N, Huang B, Zhou Y, Hao S, Zeng X. Modified heparin inhibits P-selectin-mediated cell adhesion of human colon carcinoma cells to immobilized platelets under dynamic flow conditions. J. Biol. Chem. 2004;279:29202–29210. doi: 10.1074/jbc.M312951200. [DOI] [PubMed] [Google Scholar]
  • 13.Wang L, Brown JR, Varki A, Esko JD. Heparin’s antiinflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L- and P-selectins. J. Clin. Invest. 2002;110:127–136. doi: 10.1172/JCI14996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Wang R, Huang J, Wei M, Zeng X. The synergy of 6-O-sulfation and N- or 3-O-sulfation of chitosan is required for efficient inhibition of Pselectin-mediated human melanoma A375 cell adhesion. Biosci. Biotechnol. Biochem. 2010;74:1697–1700. doi: 10.1271/bbb.100140. [DOI] [PubMed] [Google Scholar]
  • 15.Holme KR, Perlin AS. Chitosan N-sulfate. A water-soluble polyelectrolyte. Carbohydr. Res. 1997;302:7–12. doi: 10.1016/s0008-6215(97)00117-1. [DOI] [PubMed] [Google Scholar]
  • 16.Focher B, Massoli A, Torri G, Gervasini A, Morazzoni F. High molecular weight chitosan 6-O-sulfate. Synthesis, ESR and NMR characterization. Macromol. Chem. Phys. 1986;187:2609–2620. [Google Scholar]
  • 17.Baumann H, Faust V. Concepts for improved regioselective placement of O-sulfo, N-sulfo, N-acetyl, and N-carboxymethyl groups in chitosan derivatives. Carbohydr. Res. 2001;331:43–57. doi: 10.1016/s0008-6215(01)00009-x. [DOI] [PubMed] [Google Scholar]
  • 18.Gao Y, Li N, Fei R, Chen Z, Zheng S, Zeng X. P-Selectinmediated acute inflammation can be blocked by chemically modified heparin, RO-heparin. Mol. Cells. 2005;19:350–355. [PubMed] [Google Scholar]
  • 19.Shodai T, Suzuki J, Kudo S, Itoh S, Terada M, Fujita S, Shimazu H, Tsuji T. Inhibition of P-selectin-mediated cell adhesion by a sulfated derivative of sialic acid. Biochem. Biophys. Res. Commun. 2003;312:787–793. doi: 10.1016/j.bbrc.2003.10.188. [DOI] [PubMed] [Google Scholar]
  • 20.Harlan JM, Winn RK. Leukocyte-endothelial interactions: Clinical trials of anti-adhesion therapy. Crit. Care Med. 2002;30:S214–219. doi: 10.1097/00003246-200205001-00007. [DOI] [PubMed] [Google Scholar]
  • 21.Fritzsche J, Alban S, Ludwig RJ, Rubant S, Boehncke WH, Schumacher G, Bendas G. The influence of various structural parameters of semisynthetic sulfated polysaccharides on the P-selectin inhibitory capacity. Biochem. Pharmacol. 2006;72:474–485. doi: 10.1016/j.bcp.2006.05.006. [DOI] [PubMed] [Google Scholar]
  • 22.Kim MS, Sung MJ, Seo SB, Yoo SJ, Lim WK, Kim HM. Water-soluble chitosan inhibits the production of pro-inflammatory cytokine in human astrocytoma cells activated by amyloid beta peptide and interleukin-1beta. Neurosci. Lett. 2002;321:105–109. doi: 10.1016/s0304-3940(02)00066-6. [DOI] [PubMed] [Google Scholar]

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