INCREASED NITRIC-OXIDE PRODUCTION ACCOMPANIED BY THE UP-REGULATION OFINDUCIBLE NITRIC-OXIDE SYNTHASE IN VASCULAR ENDOTHELIUM FROM PATIENTSWITH SYSTEMIC LUPUS-ERYTHEMATOSUS
Hm. Belmont et al., INCREASED NITRIC-OXIDE PRODUCTION ACCOMPANIED BY THE UP-REGULATION OFINDUCIBLE NITRIC-OXIDE SYNTHASE IN VASCULAR ENDOTHELIUM FROM PATIENTSWITH SYSTEMIC LUPUS-ERYTHEMATOSUS, Arthritis and rheumatism, 40(10), 1997, pp. 1810-1816
Objective. To investigate whether systemic lupus erythematosus (SLE) i
s accompanied by increased serum nitrite levels, whether active compar
ed with inactive disease is associated with greater nitric oxide (NO)
production, and whether endothelial cells or keratinocytes serve as ce
llular sources of NO by virtue of their increased expression of either
constitutive nitric oxide synthase (cNOS) or inducible NOS (iNOS). Me
thods. Fifty-one serum samples (46 from patients with SLE) were analyz
ed for NO production by measuring nitrite levels in a calorimetric ass
ay, Skin biopsy samples from 21 SLE patients-and 11 healthy volunteers
were evaluated immunohistochemically, using monoclonal antibodies, fo
r endothelial cell and keratinocyte cNOS and iNOS expression. Results.
Serum nitrite levels were significantly elevated in the 46 patients w
ith SLE (mean +/- SEM 37 +/- 6 mu M/liter) compared with controls (15
+/- 7 mu M/liter; P < 0.01), and were elevated in patients with active
SLE compared with those with inactive disease (46 +/- 7 mu M/liter ve
rsus 30 +/- 7 mu M/liter; P < 0.01), Serum nitrite levels correlated w
ith disease activity (r = 0.47, P = 0.04) and with levels of antibodie
s to double-stranded DNA (r = 0.35, P = 0.02). Endothelial cell expres
sion of iNOS in SLE patients (mean +/- SEM score 1.5 +/- 0.2) was sign
ificantly greater compared with controls (0.6 +/- 0.2; P < 0.01), and
higher in patients with active disease compared with those with inacti
ve SLE (1.7 +/- 0.2 versus 1.2 +/- 0.2; P < 0.01), Keratinocyte expres
sion of iNOS was also significantly elevated in SLE patients (0.9 +/-
0.1) compared with controls (0.4 +/- 0.1; P < 0.001), With regard to e
xpression of cNOS, there were no differences between patients with act
ive SLE, those with inactive SLE, and normal controls in either the va
scular endothelium or the keratinocytes. Conclusion. NO production is
increased in patients with SLE, and 2 potential sources of excessive N
O are activated endothelial cells and keratinocytes via up-regulated i
NOS.