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Research ArticleOriginal Article
Open Access

Simvastatin inhibits neutrophil degranulation induced by anti-neutrophil cytoplasm auto-antibodies and N-formyl-methionine-leucine-phenylalanine (fMLP) peptide

Bahjat Al-Ani
Saudi Medical Journal May 2013, 34 (5) 477-483;
Bahjat Al-Ani
Department of Physiology, College of Medicine, King Khalid University, Abha 61421, Kingdom of Saudi Arabia. Tel. +966 (7) 2418818. E-mail: [email protected]
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Abstract

OBJECTIVE: To test the hypothesis that simvastatin is capable of blocking human neutrophil degranulation induced by proteinase 3 (PR3)-anti-neutrophil cytoplasm auto-antibodies (ANCA) and myeloperoxidase (MPO)-ANCA, and by the chemotactic and inflammatory peptide N-formyl-methionine-leucine-phenylalanine (fMLP).

METHODS: This study was conducted between March 2010 and September 2011 at the Renal Institute of Birmingham, University of Birmingham, Birmingham, United Kingdom. Immunoglobulin G (IgG) was purified from the plasma of 20 randomly selected patients with ANCA-associated vasculitis (10 PR3- and 10 MPO-ANCA), and their ability to induce neutrophil degranulation in the presence or absence of simvastatin (10 uM) was tested. The ability of the same dose of simvastatin to block fMLP-induced neutrophil degranulation was also tested. In addition, the ability of serum obtained from rats that received simvastatin at a dose of 25 mg/kg/day to block neutrophil degranulation in vitro was tested.

RESULTS: The addition of simvastatin significantly inhibited ANCA IgG-induced neutrophil degranulation by 48% (p=0.02). There was no significant difference in response to simvastatin inhibition (p=0.73) between PR3- and MPO-ANCA. Simvastatin also inhibited neutrophil degranulation induced by 1 uM fMLP (30%, p=0.04). We further demonstrated that serum from rats that received simvastatin significantly inhibited neutrophil degranulation induced by ANCA (31.7%, p=0.01) and fMLP (23.5%, p=0.03) compared to serum from control animals.

CONCLUSION: Simvastatin blocked both ANCA and fMLP-induced neutrophil degranulation. It is worth pursuing further therapeutic investigation of statins in vascular inflammatory diseases that involve neutrophil degranulation in their pathogenesis.

  • Copyright: © Saudi Medical Journal

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Saudi Medical Journal: 34 (5)
Saudi Medical Journal
Vol. 34, Issue 5
1 May 2013
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Simvastatin inhibits neutrophil degranulation induced by anti-neutrophil cytoplasm auto-antibodies and N-formyl-methionine-leucine-phenylalanine (fMLP) peptide
Bahjat Al-Ani
Saudi Medical Journal May 2013, 34 (5) 477-483;

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Simvastatin inhibits neutrophil degranulation induced by anti-neutrophil cytoplasm auto-antibodies and N-formyl-methionine-leucine-phenylalanine (fMLP) peptide
Bahjat Al-Ani
Saudi Medical Journal May 2013, 34 (5) 477-483;
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© 2025 Saudi Medical Journal Saudi Medical Journal is copyright under the Berne Convention and the International Copyright Convention.  Saudi Medical Journal is an Open Access journal and articles published are distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC). Readers may copy, distribute, and display the work for non-commercial purposes with the proper citation of the original work. Electronic ISSN 1658-3175. Print ISSN 0379-5284.

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