Persistence of early crosslink-dependent signal transduction events in human basophils after desensitization

Jane Warner, Donald Macglashan

Research output: Contribution to journalArticle

Abstract

Desensitization of human basophils with anti-IgE antibody or antigen induced an increased sensitivity to the phorbol ester TPA, evidenced as 2-5 fold increase in the potency of TPA to induce histamine release. As noted in previous publications the magnitude of the change in sensitivity to TPA was a function of the extent of cell surface IgE crosslinking. Thus, the density of cell surface antigen-specific IgE determined the magnitude of the curve shift and the multivalent antigen, BPO21-HSA was found to produce a greater curve shift than the simpler bivalent hapten, BPO2, in accord with previous studies which demonstrated that BPO2 was a "weak" stimulus compared to BPO21-HSA. Basophils which had been fully desensitized by prior treatment with anti-IgE or antigen in the absence of calcium also displayed the curve shift for at least 24 h after desensitization. However, the change induced by crosslinking which altered the cells' sensitivity to TPA required the continued presence of crosslinks and was therefore not the result of a permanent alteration induced by desensitization. Basophils which were fully desensitized to BPO7-HSA demonstrated the curve shift provided that the antigen-induced crosslinks were maintained: treatment with monovalent hapten, BPO-EACA, rapidly returned the cell response to TPA to control, non-desensitized, levels. Since TPA is thought to act by activation of protein kinase C (PKC) we demonstrated that BPO-HSA induced crosslinking increased PKC activity and that the increased activity persisted unless antigen-induced crosslinks were dissociated by the addition of monovalent hapten. These data suggest that some early activation events are not altered by the process of desensitization and can be maintained at an increased level of activity indefinitely but require the maintenance of IgE crosslinks.

Original languageEnglish (US)
Pages (from-to)129-137
Number of pages9
JournalImmunology Letters
Volume18
Issue number2
DOIs
StatePublished - 1988

Fingerprint

Basophils
Signal Transduction
Haptens
Antigens
Immunoglobulin E
Protein Kinase C
Histamine Release
Phorbol Esters
Surface Antigens
Maintenance
Calcium

Keywords

  • Desensitization
  • Human basophils
  • Phorbol esters
  • Protein kinase C

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Persistence of early crosslink-dependent signal transduction events in human basophils after desensitization. / Warner, Jane; Macglashan, Donald.

In: Immunology Letters, Vol. 18, No. 2, 1988, p. 129-137.

Research output: Contribution to journalArticle

@article{1556e733d087465789c9f6763662b85e,
title = "Persistence of early crosslink-dependent signal transduction events in human basophils after desensitization",
abstract = "Desensitization of human basophils with anti-IgE antibody or antigen induced an increased sensitivity to the phorbol ester TPA, evidenced as 2-5 fold increase in the potency of TPA to induce histamine release. As noted in previous publications the magnitude of the change in sensitivity to TPA was a function of the extent of cell surface IgE crosslinking. Thus, the density of cell surface antigen-specific IgE determined the magnitude of the curve shift and the multivalent antigen, BPO21-HSA was found to produce a greater curve shift than the simpler bivalent hapten, BPO2, in accord with previous studies which demonstrated that BPO2 was a {"}weak{"} stimulus compared to BPO21-HSA. Basophils which had been fully desensitized by prior treatment with anti-IgE or antigen in the absence of calcium also displayed the curve shift for at least 24 h after desensitization. However, the change induced by crosslinking which altered the cells' sensitivity to TPA required the continued presence of crosslinks and was therefore not the result of a permanent alteration induced by desensitization. Basophils which were fully desensitized to BPO7-HSA demonstrated the curve shift provided that the antigen-induced crosslinks were maintained: treatment with monovalent hapten, BPO-EACA, rapidly returned the cell response to TPA to control, non-desensitized, levels. Since TPA is thought to act by activation of protein kinase C (PKC) we demonstrated that BPO-HSA induced crosslinking increased PKC activity and that the increased activity persisted unless antigen-induced crosslinks were dissociated by the addition of monovalent hapten. These data suggest that some early activation events are not altered by the process of desensitization and can be maintained at an increased level of activity indefinitely but require the maintenance of IgE crosslinks.",
keywords = "Desensitization, Human basophils, Phorbol esters, Protein kinase C",
author = "Jane Warner and Donald Macglashan",
year = "1988",
doi = "10.1016/0165-2478(88)90053-3",
language = "English (US)",
volume = "18",
pages = "129--137",
journal = "Immunology Letters",
issn = "0165-2478",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Persistence of early crosslink-dependent signal transduction events in human basophils after desensitization

AU - Warner, Jane

AU - Macglashan, Donald

PY - 1988

Y1 - 1988

N2 - Desensitization of human basophils with anti-IgE antibody or antigen induced an increased sensitivity to the phorbol ester TPA, evidenced as 2-5 fold increase in the potency of TPA to induce histamine release. As noted in previous publications the magnitude of the change in sensitivity to TPA was a function of the extent of cell surface IgE crosslinking. Thus, the density of cell surface antigen-specific IgE determined the magnitude of the curve shift and the multivalent antigen, BPO21-HSA was found to produce a greater curve shift than the simpler bivalent hapten, BPO2, in accord with previous studies which demonstrated that BPO2 was a "weak" stimulus compared to BPO21-HSA. Basophils which had been fully desensitized by prior treatment with anti-IgE or antigen in the absence of calcium also displayed the curve shift for at least 24 h after desensitization. However, the change induced by crosslinking which altered the cells' sensitivity to TPA required the continued presence of crosslinks and was therefore not the result of a permanent alteration induced by desensitization. Basophils which were fully desensitized to BPO7-HSA demonstrated the curve shift provided that the antigen-induced crosslinks were maintained: treatment with monovalent hapten, BPO-EACA, rapidly returned the cell response to TPA to control, non-desensitized, levels. Since TPA is thought to act by activation of protein kinase C (PKC) we demonstrated that BPO-HSA induced crosslinking increased PKC activity and that the increased activity persisted unless antigen-induced crosslinks were dissociated by the addition of monovalent hapten. These data suggest that some early activation events are not altered by the process of desensitization and can be maintained at an increased level of activity indefinitely but require the maintenance of IgE crosslinks.

AB - Desensitization of human basophils with anti-IgE antibody or antigen induced an increased sensitivity to the phorbol ester TPA, evidenced as 2-5 fold increase in the potency of TPA to induce histamine release. As noted in previous publications the magnitude of the change in sensitivity to TPA was a function of the extent of cell surface IgE crosslinking. Thus, the density of cell surface antigen-specific IgE determined the magnitude of the curve shift and the multivalent antigen, BPO21-HSA was found to produce a greater curve shift than the simpler bivalent hapten, BPO2, in accord with previous studies which demonstrated that BPO2 was a "weak" stimulus compared to BPO21-HSA. Basophils which had been fully desensitized by prior treatment with anti-IgE or antigen in the absence of calcium also displayed the curve shift for at least 24 h after desensitization. However, the change induced by crosslinking which altered the cells' sensitivity to TPA required the continued presence of crosslinks and was therefore not the result of a permanent alteration induced by desensitization. Basophils which were fully desensitized to BPO7-HSA demonstrated the curve shift provided that the antigen-induced crosslinks were maintained: treatment with monovalent hapten, BPO-EACA, rapidly returned the cell response to TPA to control, non-desensitized, levels. Since TPA is thought to act by activation of protein kinase C (PKC) we demonstrated that BPO-HSA induced crosslinking increased PKC activity and that the increased activity persisted unless antigen-induced crosslinks were dissociated by the addition of monovalent hapten. These data suggest that some early activation events are not altered by the process of desensitization and can be maintained at an increased level of activity indefinitely but require the maintenance of IgE crosslinks.

KW - Desensitization

KW - Human basophils

KW - Phorbol esters

KW - Protein kinase C

UR - http://www.scopus.com/inward/record.url?scp=0023900922&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023900922&partnerID=8YFLogxK

U2 - 10.1016/0165-2478(88)90053-3

DO - 10.1016/0165-2478(88)90053-3

M3 - Article

VL - 18

SP - 129

EP - 137

JO - Immunology Letters

JF - Immunology Letters

SN - 0165-2478

IS - 2

ER -