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Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-induced cell death of the neutrophils

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Abstract

Anti-neutrophil cytoplasmic antibodies (ANCA) not only are triggered by target protein myeloperoxidase (MPO) and proteinase 3 (PR3) of polymorphonuclear neutrophil (PMN) but also react with primed PMN to exert the inflammatory process in vasculitis syndrome. To clarify the crucial role of PMN in ANCA-associated vasculitis and the related mechanism, PMN was cultured with monoclonal antibody MPO–ANCA and PR3–ANCA to determine the function of phagocytosis, Interleukin- 8 (IL-8) production, glucose uptake, and TNF-related apoptosis induced ligand (TRAIL) production. The spontaneous membrane expression of MPO and PR3 on PMN could be significantly increased by lipopolysaccharide (LPS) and TNF-α, but not by IL-8 or GRO-α. The PMN-stimulating activity of ANCA was demonstrated by enhancing phagocytosis, IL-8 production, and glucose uptake that was more prominent by MPO–ANCA. The PMN stimulation by ANCA was not through protein kinase, H2O2, or superoxide anion radicals as their inhibitors exerted no effect on ANCA-mediated activation. On the other hand, ANCA also accelerated PMN apoptosis and increased TRAIL production. These results demonstrate that activation-induced cell death (AICD) mechanism could be initiated in PMN with existence of ANCA. In conclusion, MPO–ANCA is more potent in stimulating PMN than PR3–ANCA. ANCA-activated PMN is not only responsible for the amplified inflammatory process in blood vessel but also initiates immune circuit via triggered macrophage/monocyte by apoptotic PMN through the mechanism of AICD elicited by ANCA.

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Abbreviations

ANCA:

Anti-neutrophil cytoplasmic autoantibody

PMN:

Human peripheral polymorphonuclear neutrophils

MPO:

Myeloperoxidase

PR3:

Proteinase-3

AICD:

Activation-induced cell death

TRAIL:

TNF-related apoptosis-induced ligand

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Acknowledgements

This study was supported by grants from National Taiwan University Hospital (92-S030), National Science Council, ROC (NSC 92-2314-B-002-115, 93-2314-B-002-088), and Yen Tjing Ling Medical Foundation (CI-92-4-2).

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Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, 7 Chung-Shan South Road, Taipei, Taiwan

    S. C. Hsieh, C. H. Wu & C. L. Yu

  2. Department of Dermatology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

    H. S. Yu

  3. Department of Laboratory Medicine, Taipei Municipal Jen-Ai Hospital, Taipei, Taiwan

    S. H. Cheng

  4. Department of Internal Medicine, Buddish Xindian-Tzu-Chi General Hospital, Taipei, Taiwan

    K. J. Li & M. C. Lu

  5. Section of Allergy, Immunology and Rheumatology, Veterans General Hospital, Taipei, Taiwan

    C. Y. Tsai

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  1. S. C. Hsieh
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Correspondence to C. L. Yu.

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Hsieh, S.C., Yu, H.S., Cheng, S.H. et al. Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-induced cell death of the neutrophils. Clin Rheumatol 26, 216–224 (2007). https://doi.org/10.1007/s10067-006-0285-3

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