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

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

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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: 23 nov. 2024. doi: https://doi.org/10.18103/mra.v11i11.4683.
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Vol 11 No 11 (2023): November Issue, Vol.11, Issue 11
Section
Research Articles

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