Rheumatology 2001; 40: 851-858
© 2001 British Society for Rheumatology
Original Papers |
Monoclonal anti-double stranded DNA antibody is a leucocyte-binding protein to up-regulate interleukin-8 gene expression and elicit apoptosis of normal human polymorphonuclear neutrophils
Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei,
1 Faculty of Medical Technology, National Yang-Ming University, Taipei,
2 Department of Medicine, Veterans General Hospital-Taipei, Taipei,
3 Department of Dermatology, Kaohsiung Medical University, Kaohsiung and
4 Department of Medicine and Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Objectives. To determine whether anti-double stranded DNA (anti-dsDNA) autoantibody could bind and affect the functions of normal human polymorphonuclear neutrophils (PMN).
Methods. Normal human PMN were incubated with different concentrations of a monoclonal mouse anti-dsDNA antibody (12B3) or mouse isotype-matched IgG2a. The binding of anti-dsDNA and PMN was measured by flow cytometry and interleukin-8 (IL-8) gene expression in PMN was detected by enzyme-linked immunosorbent assay (ELISA) and reverse transcription–polymerase chain reaction (RT–PCR). PMN apoptosis was justified by morphological changes. The cognate antigen(s) of anti-dsDNA on the PMN surface was identified by membrane biotinylation, immunoprecipitation and Western blot.
Results. The binding of PMN with anti-dsDNA was much higher than with non-specific mouse IgG2a (70.8 vs 2.0%). Anti-dsDNA at concentrations higher than 12.5 ng/ml significantly enhanced the production and mRNA expression of IL-8 by PMN. However, anti-dsDNA facilitated PMN apoptosis after 3 h incubation. Western blot analysis of biotinylated PMN cell lysates demonstrated that a 50–52 kDa membrane molecule is the cognate antigen of anti-dsDNA.
Conclusions. Anti-dsDNA autoantibody up-regulates IL-8 gene expression and elicits activation-induced cell death (AICD) of human PMN via binding to a 50–52 kDa membrane-expressed molecule.
KEY WORDS: Monoclonal anti-dsDNA antibody, Polymorphonuclear neutrophils, Interleukin-8, Apoptosis, Activation-induced cell death.
Correspondence to: C.-L. Yu, Department of Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan 100.
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