Role of Integrins Involved in Mn2+-Dependent Adhesion to Fibronectin Peptide of Mastocytoma P-815 Cells and Peritoneal Mast Cells

Article Sidebar

PDF Download
Published Nov 29, 2023
DOI: https://doi.org/10.18103/mra.v11i11.4683

Downloads

Download data is not yet available.

Submit your own article

Register as an author to reserve your spot in the next issue of the Medical Research Archives.

Author Registration

Join the Society

The European Society of Medicine is more than a professional association. We are a community. Our members work in countries across the globe, yet are united by a common goal: to promote health and health equity, around the world.

Join Europe’s leading medical society and discover the many advantages of membership, including free article publication.

Membership

Main Article Content

Yasuyo Okada
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan.
Kiyomi Ueyama
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan.
Jyun-ichi Nishikawa
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan.
Atsushi Ichikawa
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan; Bio-Education Laboratory, Tawara Building #702, 1-21-33 Higashinakajima, Osaka 533-0033, Japan.

Abstract

Mn2+-dependent integrin-mediated adhesion to the extracellular matrix is extensively studied, however, its implication in mast cell biology remains unexplored. This study aims to investigate the role of Mn2+ in promoting adhesion in mouse mastocytoma P-815 cells (P-815) and peritoneal mast cells (PMC) to the Arg-Gly-Asp (RGD)-enriched fibronectin peptide (RGD matrix) within the culture medium. Our findings indicate that Mn2+ induces cell adhesion, with optimal results achieved when P-815 were exposed to 2 mM Mn2+ for 30 min at 37ºC, resulting in approximately 40% cell adhesion to the RGD matrix. The Mn2+-dependent P-815 adhesion was inhibited by anti-integrin α4, β1, and β3 subunit function-blocking antibodies, and by the integrin αIIbβ3 antagonist tirofiban, indicating the involvement of integrins α4β1 and αIIbβ3. Similarly, Mn2+-dependent PMC adhesion to the RGD matrix was inhibited by anti-integrin α4, α5, β1, β3, and β7 subunit function-blocking antibodies and tirofiban, demonstrating the involvement of integrins α4β1, α4β7, α5β1, and αIIbβ3. Integrins α4β1 and αIIbβ3 were consistently involved in Mn2+-induced adhesion reactions in both P-815 and PMC, while integrins α4β7 and α5β1 were specifically implicated in the response to PMC only. The addition of the actin inhibitor cytochalasin D, glycosylphosphatidylinositol-anchored protein (GPI-AP) cleaving enzyme phosphatidylinositol-specific phospholipase C, and the PKA inhibitor H-89 significantly reduced Mn2+-dependent P-815 adhesion to the RGD matrix. However, adding the myosin II inhibitor brebbistatin and the RhoA inhibitor Y27632 did not produce the same effect. Furthermore, cellular cholesterol removal with 6-O-α-maltosyl-β cyclodextrin significantly diminished Mn2+-dependent P-815 adhesion, concomitant with a decrease in the expression of integrin α4 and β1 subunits on the cell surface.


 


In summary, Mn2+ fosters adhesion to the RGD matrix through integrins α4β1 and αIIbβ3, which are common between P-815 and PMC, while integrins α4β7 and α5β1 are specifically involved in PMC adhesion. The Mn2+-induced adhesion reaction in P-815 closely correlates with signal expression, including cAMP/PKA, GPI-AP, cellular cholesterol, and actin cytoskeleton, demonstrating a correlation between Mn2+-induced P-815 adhesion and signaling pathways within lipid rafts. These results may clarify questions regarding adhesion and detachment of mast cells to the extracellular matrix involved in metal ion-induced immunity and inflammation suppression.

Keywords: manganese, integrin, cell adhesion, mastocytoma P-815 cells, mast cells, lipid rafts

Article Details

How to Cite
OKADA, Yasuyo et al. Role of Integrins Involved in Mn2+-Dependent Adhesion to Fibronectin Peptide of Mastocytoma P-815 Cells and Peritoneal Mast Cells. Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4683>. Date accessed: 16 may 2024. doi: https://doi.org/10.18103/mra.v11i11.4683.
ABNT APA BibTeX CBE EndNote - EndNote format (Macintosh & Windows) MLA ProCite - RIS format (Macintosh & Windows) RefWorks Reference Manager - RIS format (Windows only) Turabian
Issue
Vol 11 No 11 (2023): November Issue, Vol.11, Issue 11
Section
Research Articles

The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.

 

References

1. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell. 2002; 110(6):673-687. doi:10.1016/S0092-8674(02)00971-6.

2. Humphries JD, Byron A, Humphries MJ. Integrin ligands at a glance. J Cell Sci. 2006; 119(19):3901-3903. doi:10.1242/jcs.03098.

3. Zhang K, Chen JF. The regulation of integrin function by divalent cations. Cell Adh Migr. 2012; 6(1):20-29. doi:10.4161/cam18702.

4. Okada Y, Nishikawa J, Semma M, Ichikawa A. Induction of integrin β3 in PGE₂-stimulated adhesion of mastocytoma P-815 cells to the Arg-Gly-Asp-enriched fragment of fibronectin. Biochem Pharmacol. 2011;81(7): 866-872. doi:10.1016/j.bcp.2011.01.010.

5. Anderson JM, Li J, Springer TA. Regulation of integrin α5β1 conformational states and intrinsic affinities by metal ions and the ADMIDAS. Mol Biol Cell. 2022;33(6): ar56:(Ar56). doi:10.1091/mbc.E21-11-0536.

6. Lietha D, Izard T. Roles of membrane domains in integrin-mediated cell adhesion. Int J Mol Sci. 2020; 21(15):5531-5549. doi:10.3390/ijms21155531.

7. Xiong JP, Stehle T, Diefenbach B, et al. Crystal structure of the extracellular segment of integrin αvβ3. Science. 2001;294(5541) :339-345. doi:10.1126/science.1064535.

8. Xiao T, Takagi J, Coller BS, Wang JH, Springer TA. Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics. Nature. 2004; 432(7013):59-67. doi:10.1038/nature02976.

9. Chen J-F, Salas A, Springer TA. Bistable regulation of integrin adhesiveness by a bipolar metal ion cluster. Nat Struct Biol. 2003; 10(12):995-1001. doi:10.1038/nsb1011.

10. Valdramidou D, Humphries MJ, Mould AP. Distinct roles of β1 metal ion-dependent adhesion site (MIDAS), adjacent to MIDAS (ADMIDAS), and ligand-associated metal-binding site (LIMBS) cation-binding sites in ligand recognition by integrin α2β1. J Biol Chem. 2008;283 (47):32704-32714. doi:10.1074/jbc.M802066200.

11. Gailit J, Ruoslahti E. Regulation of the fibronectin receptor affinity by divalent cations. J Biol Chem. 1988; 263(26):12927-12932. doi:10.1016/S0021-9258(18)37650-6.

12. Xiong JP, Stehle T, Zhang R, et al. Crystal structure of the extracellular segment of integrin αvβ3 in complex with an Arg–Gly–Asp ligand. Science. 2002; 296(5565):151-155. doi:10.1126/science.1069040.

13. Zhu J, Zhu J, Springer TA. Complete integrin headpiece opening in eight steps. J Cell Biol. 2013; 201(7):1053-1068. doi:10.1083/jcb.201212037.

14. Brown DA, London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem. 2000; 275(23):17221-17224. doi:10.1074/jbc.R000005200.

15. Krystel-Whittemore M, Dileepan KN, Wood JG. Mast cell: a multi-functional master cell. Front Immunol 2016; 6:620. doi:10.3389/fimmu.2015.00620.

16. Leist M, Sünder CA, Drube S, et al. Membrane-bound stem cell factor is the major but not only driver of fibroblast-induced murine skin mast cell differentiation. Exp Dermatol. 2017; 26(3):255-262. doi:10.1111/exd.13206. Epub February 9 2017.

17. Hatae N, Kita A, Tanaka S, Sugimoto Y, Ichikawa A. Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP4. J Biol Chem. 2003; 278(20):17977-17981. doi:10.1074/jbc.M301312200.

18. Misiak-Tłoczek A, Brzezińska-Błaszczyk E. The regulation of mast cell migration. Part 1: cell adhesion molecules. Postepy Hig Med Dosw (Online). 2007;61:485-492.

19. Pastwińska J, Walczak-Drzewiecka A, Kozłowska E, Harunari E, Ratajewski M, Dastych J. Hypoxia modulates human mast cell adhesion to hyaluronic acid. Immunol Res.2022;70(2):152-160. doi:10.1007/s12026-021-09228-x.

20. Tegoshi T, Nishida M, Arizono N. Expression and role of E-cadherin and CD103β7 (αEβ7 integrin) on cultured mucosal-type mast cells. APMIS. 2005; 113(2):91-98. doi:10.1111/j.1600-0463.2005.apm1130202.x.

21. Kuppe A, Evans LM, McMillen DA, Griffith OH. Phosphatidylinositol-specific phospholipase C of Bacillus cereus: cloning, sequencing, and relationship to other phospholipases. J Bacteriol. 1989; 171 (11):6077-6083. doi:10.1128/jb.171.11.6077-6083.1989.

22. Okada Y, Kubota Y, Koizumi K, Hizukuri S, Ohfuji T, Ogata K. Some properties and the inclusion behavior of branched cyclodextrins. Chem Pharm Bull (Tokyo). 1988; 36(6):2176-2185. doi:10.1248/cpb.36.2176.

23. Sakanaka M, Tanaka S, Sugimoto Y, Ichikawa A. Essential role of EP3 subtype in prostaglandin E2-induced adhesion of mouse cultured and peritoneal mast cells to the Arg–Gly–Asp-enriched matrix. Am J Physiol Cell Physiol. 2008; 295 (5):C1427-C1433. doi:10.1152/ajpcell.00218.2008.

24. Okada Y, Ueyama K, Nishikawa J, Semma M, Ichikawa A. Effect of 6-O-α-maltosyl-β cyclodextrin and its cholesterol inclusion complex on cellular cholesterol levels and ABCA1 and ABCG1 expression in mouse mastocytoma P-815 cells. Carbohydr Res. 2012;357:68-74. doi:10.1016/j.carres.2012.04.019.

25. Okada Y, Nishikawa J, Semma M, Ichikawa A. Role of lipid raft components and actin cytoskeleton in fibronectin-binding, surface expression, and de novo synthesis of integrin subunits in PGE2- or 8-Br-cAMP-stimulated mastocytoma P-815 cells. Biochem Pharmacol. 2014; 88(3) 364-371. doi:10.1016/j.bcp.2014.01.039.

26. Pettit LD, Powell KJ. IUPAC Stability Constant Database, IUPAC/Academic Software. Otley, United Kingdom; 2003.

27. Schliwa M. Action of cytochalasin D on cytoskeletal networks. J Cell Biol. 1982; 92:79-91(1). doi:10.1083/jcb.92.1.79.

28. Raslan Z, Magwenzi S, Aburima A, Taskén K, Naseem KM. Targeting of type I protein kinase A to lipid rafts is required for platelet inhibition by the 3′,5′-cyclic adenosine monophosphate-signaling pathway. J Thromb Haemost. 2015; 13(9) 1721-1734. doi:10.1111/jth.13042.

29. Cheung AY, Li C, Zou YJ, Wu HM. Glycosylphosphatidylinositol anchoring: control through modification. Plant Physiol. 2014; 166(2):748-750. doi:10.1104/pp.114.246926.

30. Sick E, Jeanne A, Schneider C, Dedieu S, Takeda K, Martiny L. CD47 update: a multifaceted actor in the tumour microenvironment of potential therapeutic interest. Br J Pharmacol. 2012; 167(7):1415-1430. doi:10.1111/j.1476-5381.2012.02099.x.

31. Kaur S, Isenberg JS, Roberts DD. CD47 (cluster of differentiation 47). Atlas Genet Cytogenet Oncol Haematol. 2021; 25(2):83-102.

32. Luo BH, Carman CV, Springer TA. Structural basis of integrin regulation and signaling. Annu Rev Immunol. 2007; 25:619-647.doi:10.1146/annurev.immunol.25.022106.141618.

33. Clark EA, Brugge JS. Integrins and signal transduction pathways: the road taken. Science. 1995; 268 (5208):233-239. doi:10.1126/science.7716514.

34. Bershadsky A, Kozlov M, Geiger B. Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize. Curr Opin Cell Biol. 2006; 18(5):472-481. doi:10.1016/j.ceb.2006.08.012.

35. Wagner M, Klein CL, van Kooten TG, Kirkpatrick CJ. Mechanisms of cell activation by heavy metal ions. J Biomed Mater Res. 1998; 42(3):443-452. doi:10.1002/(sici)1097-4636(19981205)42:3<443::aid-jbm14>3.0.co;2-h.

36. Mould AP, Humphries MJ. Regulation of integrin function through conformational complexity: not simply a knee-jerk reaction? Curr Opin Cell Biol. 2004; 16(5):544-551. doi:10.1016/j.ceb.2004.07.003.

37. Oki T, Kitaura J, Eto K, et al. Integrin αIIbβ3 induces the adhesion and activation of mast cells through interaction with fibrinogen. J Immunol. 2006; 176(1):52-60. doi:10.4049/jimmunol.176.1.52.

38. Malbec O, Roget K, Schiffer C, et al. Peritoneal cell-derived mast cells: an in vitro model of mature serosal-type mouse mast cells. J Immunol. 2007; 178(10):6465-6475. doi:10.4049/jimmunol.178.10.6465.

39. Bodin S, Soulet C, Tronchère H, et al. Integrin-dependent interaction of lipid rafts with the actin cytoskeleton in activated human platelets. J Cell Sci. 2005; 118(4):759-769. doi:10.1242/jcs.01648.

40. Bi J, Wang R, Zeng X. Lipid rafts regulate the lamellipodia formation of melanoma A375 cells via actin cytoskeleton-mediated recruitment of β1 and β3 integrin. Oncol Lett. 2018;16(5):6540-6546. doi:10.3892/ol.2018.9466.

41. Zaidel-Bar R, Cohen M, Addadi L, Geiger B. Hierarchical assembly of cell-matrix adhesion complexes. Biochem Soc Trans. 2004;32():416-420. doi:10.1042/BST0320416.

42. Zimerman B, Volberg T, Geiger B. Early molecular events in the assembly of the focal adhesion-stress fiber complex during fibroblast spreading. Cell Motil Cytoskeleton. 2004; 58(3):143-159. doi:10.1002/cm.20005.

43. Zhu G, Liu Y, Zhi Y, et al. PKA- and Ca2+-dependent p38 MAPK/CREB activation protects against manganese-mediated neuronal apoptosis. Toxicol Lett. 2019;309:10-19. doi:10.1016/j.toxlet.2019.04.004.

44. Knape MJ, Ballez M, Burghardt NC, et al. Divalent metal ions control activity and inhibition of protein kinases. Metallomics. 2017;9(11):1576-1584. doi:10.1039/c7mt00204a.

45. Howe AK. Regulation of actin-based cell migration by cAMP/PKA. Biochim Biophys Acta. 2004; 1692 (2-3):159-174. doi:10.1016/j.bbamcr.2004.03.005.

46. Lim CJ, Kain KH, Tkachenko E, et al. Integrin-mediated protein kinase A activation at the leading edge of migrating cells. Mol Biol Cell. 2008; 19(11):4930-4941. doi:10.1091/mbc.e08-06-0564.

47. Thomas L, Byers HR, Vink J, Stamenkovic I. CD44H regulates tumor cell migration on hyaluronate-coated substrate. J Cell Biol. 1992;118(4):971-977. doi:10.1083/jcb.118.4.971.

48. Bhadriraju K, Yang M, Alom Ruiz SA, Pirone D, Tan J, Chen CS. Activation of ROCK by RhoA is regulated by cell adhesion, shape, and cytoskeletal tension. Exp Cell Res. 2007; 313(16):3616-3623. doi:10.1016/j.yexcr.2007.07.002.

49. Schiller HB, Hermann MR, Polleux J, et al. β1- and αv-class integrins cooperate to regulate myosin II during rigidity sensing of fibronectin-based microenvironments. Nat Cell Biol. 2013; 15(6):625-636. doi:10.1038/ncb2747.

50. Povlsen GK, Ditlevsen DK. The neural cell adhesion molecule NCAM and lipid rafts. Adv Exp Med Biol. 2010; 663:183-198. doi:10.1007/978-1-4419-1170-4_12.

51. Wang R, Bi J, Ampah KK, Ba X, Liu W, Zeng X. Lipid rafts control human melanoma cell migration by regulating focal adhesion disassembly. Biochim Biophys Acta. 2013; 1833(12):3195-3205. doi:10.1016/j.bbamcr.2013.09.007.