Eosinophil major basic protein induces degranulation and IL-8 production by human eosinophils

H. Kita, R. I. Abu-Ghazaleh, Sanjiv Sur, G. J. Gleich

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Eosinophil granule proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), and eosinophil cationic protein (ECP), possess a wide range of biologic activities including the ability to activate other cells, such as basophils, neutrophils, and platelets. Here we have analyzed the effects of these proteins on eosinophils themselves. MBP and EPO, at concentrations as low as 0.1 μg/ml, induced eosinophil degranulation as measured by release of eosinophil-derived neurotoxin (EDN); in contrast, ECP, at 1 μg/ml, was inactive. MBP (10 μg/ml) and EPO (0.1 μg/ml) induced EDN release comparable with one of the strongest agonists for eosinophils, secretory IgA. Pretreatment of cells with dibutyryl cAMP or cytochalasin B completely abolished the EDN release induced by MBP and EPO, suggesting that the effects of MBP and EPO are not due to cytotoxic lysis of the cells. Degranulation induced by MBP was only partially dependent on calcium, and no elevation of intracellular Ca2+ concentration ([Ca2+](i)) was observed in eosinophils stimulated with MBP. MBP stimulated the production, up to eightfold, of IL-8 by eosinophils in a dose-dependent manner. The MBP-stimulated expression of IL-8 mRNA by eosinophils was confirmed by reverse transcription-PCR. The MBP- stimulated production of IL-8 was inhibited by actinomycin D, but not by cyclosporin A. Furthermore, MBP and calcium ionophore ionomycin synergistically induced production of leukotriene C4 from eosinophils. Thus, MBP and EPO may act as autocrine mediators in the pathogenesis of eosinophil- associated diseases, such as bronchial asthma.

Original languageEnglish (US)
Pages (from-to)4749-4758
Number of pages10
JournalJournal of Immunology
Volume154
Issue number9
StatePublished - 1995
Externally publishedYes

Fingerprint

Eosinophil Major Basic Protein
Interleukin-8
Eosinophils
Eosinophil Peroxidase
Proteins
Eosinophil-Derived Neurotoxin
Eosinophil Cationic Protein
Eosinophil Granule Proteins
Secretory Immunoglobulin A
Leukotriene C4
Cytochalasin B
Ionomycin
Basophils
Calcium Ionophores
Dactinomycin

ASJC Scopus subject areas

  • Immunology

Cite this

Kita, H., Abu-Ghazaleh, R. I., Sur, S., & Gleich, G. J. (1995). Eosinophil major basic protein induces degranulation and IL-8 production by human eosinophils. Journal of Immunology, 154(9), 4749-4758.

Eosinophil major basic protein induces degranulation and IL-8 production by human eosinophils. / Kita, H.; Abu-Ghazaleh, R. I.; Sur, Sanjiv; Gleich, G. J.

In: Journal of Immunology, Vol. 154, No. 9, 1995, p. 4749-4758.

Research output: Contribution to journalArticle

Kita, H, Abu-Ghazaleh, RI, Sur, S & Gleich, GJ 1995, 'Eosinophil major basic protein induces degranulation and IL-8 production by human eosinophils', Journal of Immunology, vol. 154, no. 9, pp. 4749-4758.
Kita, H. ; Abu-Ghazaleh, R. I. ; Sur, Sanjiv ; Gleich, G. J. / Eosinophil major basic protein induces degranulation and IL-8 production by human eosinophils. In: Journal of Immunology. 1995 ; Vol. 154, No. 9. pp. 4749-4758.
@article{6926ad1f90bb4fa5bfdbc46e721e6411,
title = "Eosinophil major basic protein induces degranulation and IL-8 production by human eosinophils",
abstract = "Eosinophil granule proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), and eosinophil cationic protein (ECP), possess a wide range of biologic activities including the ability to activate other cells, such as basophils, neutrophils, and platelets. Here we have analyzed the effects of these proteins on eosinophils themselves. MBP and EPO, at concentrations as low as 0.1 μg/ml, induced eosinophil degranulation as measured by release of eosinophil-derived neurotoxin (EDN); in contrast, ECP, at 1 μg/ml, was inactive. MBP (10 μg/ml) and EPO (0.1 μg/ml) induced EDN release comparable with one of the strongest agonists for eosinophils, secretory IgA. Pretreatment of cells with dibutyryl cAMP or cytochalasin B completely abolished the EDN release induced by MBP and EPO, suggesting that the effects of MBP and EPO are not due to cytotoxic lysis of the cells. Degranulation induced by MBP was only partially dependent on calcium, and no elevation of intracellular Ca2+ concentration ([Ca2+](i)) was observed in eosinophils stimulated with MBP. MBP stimulated the production, up to eightfold, of IL-8 by eosinophils in a dose-dependent manner. The MBP-stimulated expression of IL-8 mRNA by eosinophils was confirmed by reverse transcription-PCR. The MBP- stimulated production of IL-8 was inhibited by actinomycin D, but not by cyclosporin A. Furthermore, MBP and calcium ionophore ionomycin synergistically induced production of leukotriene C4 from eosinophils. Thus, MBP and EPO may act as autocrine mediators in the pathogenesis of eosinophil- associated diseases, such as bronchial asthma.",
author = "H. Kita and Abu-Ghazaleh, {R. I.} and Sanjiv Sur and Gleich, {G. J.}",
year = "1995",
language = "English (US)",
volume = "154",
pages = "4749--4758",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - Eosinophil major basic protein induces degranulation and IL-8 production by human eosinophils

AU - Kita, H.

AU - Abu-Ghazaleh, R. I.

AU - Sur, Sanjiv

AU - Gleich, G. J.

PY - 1995

Y1 - 1995

N2 - Eosinophil granule proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), and eosinophil cationic protein (ECP), possess a wide range of biologic activities including the ability to activate other cells, such as basophils, neutrophils, and platelets. Here we have analyzed the effects of these proteins on eosinophils themselves. MBP and EPO, at concentrations as low as 0.1 μg/ml, induced eosinophil degranulation as measured by release of eosinophil-derived neurotoxin (EDN); in contrast, ECP, at 1 μg/ml, was inactive. MBP (10 μg/ml) and EPO (0.1 μg/ml) induced EDN release comparable with one of the strongest agonists for eosinophils, secretory IgA. Pretreatment of cells with dibutyryl cAMP or cytochalasin B completely abolished the EDN release induced by MBP and EPO, suggesting that the effects of MBP and EPO are not due to cytotoxic lysis of the cells. Degranulation induced by MBP was only partially dependent on calcium, and no elevation of intracellular Ca2+ concentration ([Ca2+](i)) was observed in eosinophils stimulated with MBP. MBP stimulated the production, up to eightfold, of IL-8 by eosinophils in a dose-dependent manner. The MBP-stimulated expression of IL-8 mRNA by eosinophils was confirmed by reverse transcription-PCR. The MBP- stimulated production of IL-8 was inhibited by actinomycin D, but not by cyclosporin A. Furthermore, MBP and calcium ionophore ionomycin synergistically induced production of leukotriene C4 from eosinophils. Thus, MBP and EPO may act as autocrine mediators in the pathogenesis of eosinophil- associated diseases, such as bronchial asthma.

AB - Eosinophil granule proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), and eosinophil cationic protein (ECP), possess a wide range of biologic activities including the ability to activate other cells, such as basophils, neutrophils, and platelets. Here we have analyzed the effects of these proteins on eosinophils themselves. MBP and EPO, at concentrations as low as 0.1 μg/ml, induced eosinophil degranulation as measured by release of eosinophil-derived neurotoxin (EDN); in contrast, ECP, at 1 μg/ml, was inactive. MBP (10 μg/ml) and EPO (0.1 μg/ml) induced EDN release comparable with one of the strongest agonists for eosinophils, secretory IgA. Pretreatment of cells with dibutyryl cAMP or cytochalasin B completely abolished the EDN release induced by MBP and EPO, suggesting that the effects of MBP and EPO are not due to cytotoxic lysis of the cells. Degranulation induced by MBP was only partially dependent on calcium, and no elevation of intracellular Ca2+ concentration ([Ca2+](i)) was observed in eosinophils stimulated with MBP. MBP stimulated the production, up to eightfold, of IL-8 by eosinophils in a dose-dependent manner. The MBP-stimulated expression of IL-8 mRNA by eosinophils was confirmed by reverse transcription-PCR. The MBP- stimulated production of IL-8 was inhibited by actinomycin D, but not by cyclosporin A. Furthermore, MBP and calcium ionophore ionomycin synergistically induced production of leukotriene C4 from eosinophils. Thus, MBP and EPO may act as autocrine mediators in the pathogenesis of eosinophil- associated diseases, such as bronchial asthma.

UR - http://www.scopus.com/inward/record.url?scp=0029030605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029030605&partnerID=8YFLogxK

M3 - Article

C2 - 7722326

AN - SCOPUS:0029030605

VL - 154

SP - 4749

EP - 4758

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -