PMID- 11511752 OWN - NLM STAT- MEDLINE DCOM- 20010927 LR - 20190513 IS - 1462-0324 (Print) IS - 1462-0324 (Linking) VI - 40 IP - 8 DP - 2001 Aug TI - 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. PG - 851-8 AB - 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. FAU - Hsieh, S C AU - Hsieh SC AD - Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. FAU - Sun, K H AU - Sun KH FAU - Tsai, C Y AU - Tsai CY FAU - Tsai, Y Y AU - Tsai YY FAU - Tsai, S T AU - Tsai ST FAU - Huang, D F AU - Huang DF FAU - Han, S H AU - Han SH FAU - Yu, H S AU - Yu HS FAU - Yu, C L AU - Yu CL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Rheumatology (Oxford) JT - Rheumatology (Oxford, England) JID - 100883501 RN - 0 (Antibodies, Antinuclear) RN - 0 (Antibodies, Monoclonal) RN - 0 (Carrier Proteins) RN - 0 (Interleukin-8) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Antibodies, Antinuclear/*physiology MH - Antibodies, Monoclonal/*immunology MH - *Apoptosis MH - Carrier Proteins/*physiology MH - DNA/*immunology MH - *Gene Expression Regulation MH - Humans MH - Interleukin-8/*genetics MH - Mice MH - Neutrophils/*physiology MH - Up-Regulation EDAT- 2001/08/21 10:00 MHDA- 2001/09/28 10:01 CRDT- 2001/08/21 10:00 PHST- 2001/08/21 10:00 [pubmed] PHST- 2001/09/28 10:01 [medline] PHST- 2001/08/21 10:00 [entrez] AID - 10.1093/rheumatology/40.8.851 [doi] PST - ppublish SO - Rheumatology (Oxford). 2001 Aug;40(8):851-8. doi: 10.1093/rheumatology/40.8.851.