PMID- 12412196
OWN - NLM
STAT- MEDLINE
DCOM- 20030402
LR  - 20170112
IS  - 0392-856X (Print)
IS  - 0392-856X (Linking)
VI  - 20
IP  - 5
DP  - 2002 Sep-Oct
TI  - Neutrophils from systemic lupus erythematosus patients demonstrate increased 
      nuclear DNA damage.
PG  - 653-60
AB  - OBJECTIVE: (i) To determine the levels of nuclear DNA damage in freshly isolated 
      and cultured neutrophils from SLE patients (SLE), rheumatoid arthritis patients 
      (RA) and healthy individuals and relate these to the percentage of apoptotic 
      neutrophils. (ii) To assess rates of repair of neutrophil oxidative DNA damage. 
      METHODS: The comet assay was used to quantify nuclear DNA damage in neutrophils 
      from SLE patients (n = 20), control subjects (n = 15) and RA patients (n = 15). 
      Levels of DNA damage were related to apoptosis as assessed by annexin V binding 
      and morphology. Rates of repair of neutrophil oxidative DNA damage was measured 
      by incorporating formamidopyrimidine-DNA glycosylase (FPG) into the comet assay. 
      RESULTS: Nuclear DNA damage in freshly isolated and cultured (20 h) neutrophils 
      was significantly greater in SLE patients (median = 12.5%, 27.3%; respectively) 
      compared with RA patients (median = 9.4%, p = 0.002; 19.3%, p = 0.002; 
      respectively) and control subjects (median = 8.2%, p = 0.003; 18.7%, p = 0.01, 
      respectively). Significantly higher levels of circulating apoptotic neutrophils 
      were demonstrated in SLE patients compared to RA and control subjects. Similar 
      findings were observed following 20 h cultured neutrophil preparations. However, 
      no significant direct correlation between neutrophil apoptosis and DNA damage was 
      observed. Neutrophils from 3 of 5 SLE patients demonstrated an impaired ability 
      to repair oxidatively modified DNA. CONCLUSION: Neutrophils from SLE patients 
      display increased DNA damage and, additionally, may demonstrate defective repair 
      of oxidative DNA damage. These features, in addition to increased rates of 
      neutrophil apoptosis, may act as contributing factors to autoantigen excess and 
      immune activation.
FAU - McConnell, J R
AU  - McConnell JR
AD  - Queen's University Musculoskeletal Education and Research Unit, Department of 
      Rheumatology, Musgrave Park Hospital, Belfast, UK.
FAU - Crockard, A D
AU  - Crockard AD
FAU - Cairns, A P
AU  - Cairns AP
FAU - Bell, A L
AU  - Bell AL
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Clin Exp Rheumatol
JT  - Clinical and experimental rheumatology
JID - 8308521
RN  - 0 (Annexin A5)
RN  - 0 (Antibodies, Antinuclear)
SB  - IM
MH  - Adult
MH  - Annexin A5/*analysis
MH  - Antibodies, Antinuclear/*analysis
MH  - *Apoptosis
MH  - Arthritis, Rheumatoid/*immunology/metabolism
MH  - Comet Assay
MH  - *DNA Fragmentation
MH  - Female
MH  - Humans
MH  - Lupus Erythematosus, Systemic/*immunology/metabolism
MH  - Male
MH  - Middle Aged
MH  - Neutrophils/*immunology/metabolism
EDAT- 2002/11/05 04:00
MHDA- 2003/04/04 05:00
CRDT- 2002/11/05 04:00
PHST- 2002/11/05 04:00 [pubmed]
PHST- 2003/04/04 05:00 [medline]
PHST- 2002/11/05 04:00 [entrez]
PST - ppublish
SO  - Clin Exp Rheumatol. 2002 Sep-Oct;20(5):653-60.