Cytotoxicity of human eosinophil granule major basic protein to human nasal sinus mucosa in vitro

Eosinophil granule major basic protein (MBP), a potent toxin for helminths and various cell types, is a 13.8-kD single polypeptide rich in arginine with a calculated isoelectric point (pI) of 10.9. A cDNA for human MBP was isolated from a gamma GT10 HL-60 cDNA library. The nucleotide sequence of the MBP cDNA indicates that MBP is translated as a 25.2-kD preproprotein. The 9.9-kD pro-portion of proMBP is rich in glutamic and aspartic acids and has a calculated pI of 3.9, while proMBP itself has a calculated pI of 6.2. We suggest that MBP is translated as a nontoxic precursor that protects the eosinophil from damage while the protein is processed through the endoplasmic reticulum to its sequestered site in the granule core toxic MBP, and we present results from the literature suggesting that other cationic toxins, which damage cell membranes, may also be processed from nontoxic precursors containing distinct anionic and cationic regions.

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198 Stimulation of basophil and mast cell histamine release by human eosinophil granule major basic protein

Journal of Allergy and Clinical Immunology ◽

10.1016/0091-6749(83)90322-6 ◽

1983 ◽

Vol 71 (1) ◽

pp. 138

Author(s):

M ODONNELL ◽

S ACKERMAN ◽

G GLEICH ◽

L THOMAS

Keyword(s):

Mast Cell ◽

Histamine Release ◽

Basic Protein ◽

Major Basic Protein ◽

Human Eosinophil ◽

Eosinophil Granule ◽

Stimulation Of

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The Effect of Human Eosinophil Granule Major Basic Protein on Airway Responsiveness in the RatIn Vivo: A Comparison with Polycations

American Review of Respiratory Disease ◽

10.1164/ajrccm/147.4.982 ◽

1993 ◽

Vol 147 (4) ◽

pp. 982-988 ◽

Cited By ~ 70

Author(s):

Derek A. Uchida ◽

Steven J. Ackerman ◽

Anthony J. Coyle ◽

Gary L. Larsen ◽

Peter F. Weller ◽

...

Keyword(s):

Basic Protein ◽

Airway Responsiveness ◽

Major Basic Protein ◽

Human Eosinophil ◽

Eosinophil Granule

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Epithelial augmentation of trachealis contraction caused by major basic protein of eosinophils

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.4.1867 ◽

1989 ◽

Vol 66 (4) ◽

pp. 1867-1873 ◽

Cited By ~ 44

Author(s):

J. D. Brofman ◽

S. R. White ◽

J. S. Blake ◽

N. M. Munoz ◽

G. J. Gleich ◽

...

Keyword(s):

Smooth Muscle ◽

Basic Protein ◽

Tracheal Smooth Muscle ◽

Active Tension ◽

Major Basic Protein ◽

Human Eosinophil ◽

Control Segment ◽

Eosinophil Granule

We studied the effect of epithelial removal and intraepithelial administration of human eosinophil granule major basic protein (MBP) on the contraction of underlying canine tracheal smooth muscle in 23 dogs in vivo. A dual in situ tracheal preparation was utilized that allowed sharp excision of epithelium. The response to intra-arterial acetylcholine (ACh) was augmented substantially in five dogs receiving 200 micrograms MBP by intraepithelial instillation. Active tension elicited by 10(-8) mol intra-arterial ACh was 34.0 +/- 2.2 g/cm before and 46.1 +/- 2.6 g/cm 30 min after MBP (P less than 0.002). There was no change in active tension in the control segment in the same dogs after intraepithelial instillation of vehicle only (34.7 +/- 3.2 vs. 34.4 +/- 2.3 g/cm; P = NS). Instillation of MBP directly into the subepithelial tracheal smooth muscle did not alter contraction. To assess whether this augmentation was caused by inhibition of an epithelial-derived relaxant factor, additional studies were performed in nine other dogs in which the epithelium was excised discretely from one of the two tracheal segments. No significant differences in contractile response to ACh or relaxation response to isoproterenol were observed at 2, 15, 30, or 60 min after epithelial excision. We demonstrate that intraepithelial administration of MBP augments the contraction of underlying canine tracheal smooth muscle elicited by ACh. This augmentation is a direct effect of MBP and does not require antagonism of epithelial inhibition.

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Low-angle shadowing and colloidal gold-labeling of liposome interaction with the eosinophil major basic protein

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123945 ◽

1992 ◽

Vol 50 (1) ◽

pp. 708-709

Author(s):

Margaret J. Hukee ◽

Randa I. Abu-Ghazaleh ◽

Franklyn G. Prendergast

Keyword(s):

Lipid Bilayers ◽

Mammalian Cells ◽

Plasma Membranes ◽

Basic Protein ◽

Direct Interaction ◽

Major Basic Protein ◽

Eosinophil Granule ◽

Spectroscopy Studies ◽

Eosinophil Major Basic Protein

The eosinophil major basic protein (MBP) has been localized in the crystalloid core of the specific eosinophil granule. High levels of MBP are present in sputa and at sites of epithelial damage in patients with brochial asthma suggesting that MBP is released from the eosinophil. In vitro, the toxicity of MBP to mammalian cells, helminths, protozoa, and bacteria, has been demonstrated. MBP also induced the degranulation of platelets, basophils, and mast cells. Since these events involve extracellular MBP and rupture of plasma membranes, the mechanism of toxicity may be due to a direct interaction between MBP and biological membranes. Fluorescence spectroscopy studies using synthetic lipid bilayers (liposomes) showed the ability of MBP to induce disorder, fusion and lysis of those membranes. In this report, structural evidence is presented for liposome aggregation and possible lysis in the presence of MBP.

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