Inhibiting phosphatase SHIP-1 enhances suboptimal IgE-mediated activation of human blood basophils but inhibits IgE-mediated activation of cultured human mast cells

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Inhibiting phosphatase SHIP-1 enhances suboptimal IgE-mediated activation of human blood basophils but inhibits IgE-mediated activation of cultured human mast cells. / Rasmussen, Pernille; Spillner, Edzard; Hoffmann, Hans Jürgen.

I: Immunology Letters, Bind 210, 01.06.2019, s. 40-46.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{6ae454833d584500a4c5f18f5cc908c2,
title = "Inhibiting phosphatase SHIP-1 enhances suboptimal IgE-mediated activation of human blood basophils but inhibits IgE-mediated activation of cultured human mast cells",
abstract = " IgE-mediated activation of basophil granulocytes and mast cells follows a bell-shaped dose-response curve. The decreased activation at supraoptimal allergen stimulation is thought to be associated with SH2-containing inositol-5′-phosphatase 1 (SHIP-1). SHIP-1 phosphorylation is inversely related to IgE-mediated releasability of basophils. This study sought to clarify the regulatory role of SHIP-1 in degranulation of basophil granulocytes and mast cells by selective inhibition of the phosphatase function of SHIP-1with 3-α-aminocholestane (3-α-AC). Six grass pollen allergic patients, six non-responder patients and six cultured human primary mast cell lines were included. The effect of 3-α-AC (1–60 μM, 30 min, 37 °C) was analyzed at individual suboptimal, optimal and supra-optimal allergen concentrations. The activity, upregulation of CD63, measured at different conditions was compared to evaluate the maximal effect of selective SHIP-1 inhibition. Basophils of five non-responder patients were treated with 3-α-AC (10 μM, 30 min, 37 °C). At high concentrations (>60 μM) of 3-α-AC, cells appeared to enter apoptosis. The median reactivity increased from 27.1% to 44.9% CD63 + basophils at 10 μM of 3-α-AC and suboptimal allergen stimulation (p = 0.0153). There was no effect on blood basophils of 3-α-AC at optimal or supra-optimal allergen concentrations. In contrast, treatment with more than 6 μM 3-α-AC significantly inhibited mast cell reactivity. 10 μM 3-α-AC reduced median reactivity from 32.85% to 16.5% CD63+ mast cells (p = 0.0465). Treatment with 3-α-AC did not increase response of basophils of non-responder patients. Modulating blood basophils with 3-α-AC enhanced reactivity only at suboptimal allergen concentration, and basophils from non-responders did not regain responsiveness to IgE stimulation. 3-α-AC inhibited the IgE response of mast cells in a dose dependent manner. ",
keywords = "Allergen-IgE activation, Basophil activation test, Human blood basophils, Human mast cells, SHIP-1",
author = "Pernille Rasmussen and Edzard Spillner and Hoffmann, {Hans J{\"u}rgen}",
year = "2019",
month = jun,
day = "1",
doi = "10.1016/j.imlet.2019.04.003",
language = "English",
volume = "210",
pages = "40--46",
journal = "Immunology Letters",
issn = "0165-2478",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Inhibiting phosphatase SHIP-1 enhances suboptimal IgE-mediated activation of human blood basophils but inhibits IgE-mediated activation of cultured human mast cells

AU - Rasmussen, Pernille

AU - Spillner, Edzard

AU - Hoffmann, Hans Jürgen

PY - 2019/6/1

Y1 - 2019/6/1

N2 - IgE-mediated activation of basophil granulocytes and mast cells follows a bell-shaped dose-response curve. The decreased activation at supraoptimal allergen stimulation is thought to be associated with SH2-containing inositol-5′-phosphatase 1 (SHIP-1). SHIP-1 phosphorylation is inversely related to IgE-mediated releasability of basophils. This study sought to clarify the regulatory role of SHIP-1 in degranulation of basophil granulocytes and mast cells by selective inhibition of the phosphatase function of SHIP-1with 3-α-aminocholestane (3-α-AC). Six grass pollen allergic patients, six non-responder patients and six cultured human primary mast cell lines were included. The effect of 3-α-AC (1–60 μM, 30 min, 37 °C) was analyzed at individual suboptimal, optimal and supra-optimal allergen concentrations. The activity, upregulation of CD63, measured at different conditions was compared to evaluate the maximal effect of selective SHIP-1 inhibition. Basophils of five non-responder patients were treated with 3-α-AC (10 μM, 30 min, 37 °C). At high concentrations (>60 μM) of 3-α-AC, cells appeared to enter apoptosis. The median reactivity increased from 27.1% to 44.9% CD63 + basophils at 10 μM of 3-α-AC and suboptimal allergen stimulation (p = 0.0153). There was no effect on blood basophils of 3-α-AC at optimal or supra-optimal allergen concentrations. In contrast, treatment with more than 6 μM 3-α-AC significantly inhibited mast cell reactivity. 10 μM 3-α-AC reduced median reactivity from 32.85% to 16.5% CD63+ mast cells (p = 0.0465). Treatment with 3-α-AC did not increase response of basophils of non-responder patients. Modulating blood basophils with 3-α-AC enhanced reactivity only at suboptimal allergen concentration, and basophils from non-responders did not regain responsiveness to IgE stimulation. 3-α-AC inhibited the IgE response of mast cells in a dose dependent manner.

AB - IgE-mediated activation of basophil granulocytes and mast cells follows a bell-shaped dose-response curve. The decreased activation at supraoptimal allergen stimulation is thought to be associated with SH2-containing inositol-5′-phosphatase 1 (SHIP-1). SHIP-1 phosphorylation is inversely related to IgE-mediated releasability of basophils. This study sought to clarify the regulatory role of SHIP-1 in degranulation of basophil granulocytes and mast cells by selective inhibition of the phosphatase function of SHIP-1with 3-α-aminocholestane (3-α-AC). Six grass pollen allergic patients, six non-responder patients and six cultured human primary mast cell lines were included. The effect of 3-α-AC (1–60 μM, 30 min, 37 °C) was analyzed at individual suboptimal, optimal and supra-optimal allergen concentrations. The activity, upregulation of CD63, measured at different conditions was compared to evaluate the maximal effect of selective SHIP-1 inhibition. Basophils of five non-responder patients were treated with 3-α-AC (10 μM, 30 min, 37 °C). At high concentrations (>60 μM) of 3-α-AC, cells appeared to enter apoptosis. The median reactivity increased from 27.1% to 44.9% CD63 + basophils at 10 μM of 3-α-AC and suboptimal allergen stimulation (p = 0.0153). There was no effect on blood basophils of 3-α-AC at optimal or supra-optimal allergen concentrations. In contrast, treatment with more than 6 μM 3-α-AC significantly inhibited mast cell reactivity. 10 μM 3-α-AC reduced median reactivity from 32.85% to 16.5% CD63+ mast cells (p = 0.0465). Treatment with 3-α-AC did not increase response of basophils of non-responder patients. Modulating blood basophils with 3-α-AC enhanced reactivity only at suboptimal allergen concentration, and basophils from non-responders did not regain responsiveness to IgE stimulation. 3-α-AC inhibited the IgE response of mast cells in a dose dependent manner.

KW - Allergen-IgE activation

KW - Basophil activation test

KW - Human blood basophils

KW - Human mast cells

KW - SHIP-1

UR - http://www.scopus.com/inward/record.url?scp=85064860285&partnerID=8YFLogxK

U2 - 10.1016/j.imlet.2019.04.003

DO - 10.1016/j.imlet.2019.04.003

M3 - Journal article

C2 - 31004680

AN - SCOPUS:85064860285

VL - 210

SP - 40

EP - 46

JO - Immunology Letters

JF - Immunology Letters

SN - 0165-2478

ER -