Activation of NF-kappaB and expression of COX-2 in association with neutrophil infiltration in systemic vascular tissue of women with preeclampsia.
OBJECTIVE
The purpose of this study was to determine whether activation of NF-kappaB and expression of COX-2 are associated with neutrophil infiltration in systemic vascular tissue of women with preeclampsia.


METHODS
Subcutaneous fat biopsies were obtained at cesarean section or abdominal surgery from preeclamptic women (n = 7), normal pregnant women (n = 6), and normal nonpregnant women (n = 5). Resistance-sized vessels (10 to 200 microm) in subcutaneous fat were evaluated using immunohistochemical staining for: (1) CD66b, a neutrophil antigen, (2) nuclear factor-kappaB (NF-kappaB), a transcription factor for genes of inflammation, and (3) cyclooxygenase-2 (COX-2), an inflammatory gene product.


RESULTS
The percentage of vessels which showed staining for CD66b, NF-kappaB, and COX-2 was significantly greater for preeclamptic patients as compared to normal nonpregnant or normal pregnant patients. In preeclamptic patients, vessel staining for NF-kappaB and COX-2 was present in both endothelium and in vascular smooth muscle. Leukocytes in the lumen and adhered to endothelium also stained for NF-kappaB and COX-2. Activation of NF-kappaB and expression of COX-2 were coincident with neutrophil flattening and adherence to endothelium and infiltration into the intimal space.


CONCLUSIONS
These data demonstrate activation of NF-kappaB and expression of COX-2 in systemic vasculature of women with preeclampsia, and they demonstrate that this vascular inflammation is linked with neutrophil infiltration. Neutrophil release of toxic substances, such as reactive oxygen species, TNFalpha and thromboxane, could be responsible for vasoconstriction and vascular dysfunction. These data clearly place preeclampsia in the category of an inflammatory disease associated with immune dysfunction.
Shah
Tanvi J
TJ
Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0034, USA.
Walsh
Scott W
SW
D000328:Adult; D001808:Blood Vessels / Q000276:immunology* / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis*; D016328:NF-kappa B / Q000502:physiology*; D020556:Neutrophil Infiltration / Q000502:physiology*; D011225:Pre-Eclampsia / Q000276:immunology* / Q000378:metabolism*; D011247:Pregnancy
D008565:Membrane Proteins; D016328:NF-kappa B; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human