ResearchObstetricsActivation of NF-κB and expression of COX-2 in association with neutrophil infiltration in systemic vascular tissue of women with preeclampsia

ObjectiveThe purpose of this study was to determine whether activation of NF-κB and expression of COX-2 are associated with neutrophil infiltration in systemic vascular tissue of women with preeclampsia.Study designSubcutaneous 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 μm) in subcutaneous fat were evaluated using immunohistochemical staining for: (1) CD66b, a neutrophil antigen, (2) nuclear factor-κB (NF-κB), a transcription factor for genes of inflammation, and (3) cyclooxygenase-2 (COX-2), an inflammatory gene product.ResultsThe percentage of vessels which showed staining for CD66b, NF-κB, 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-κB 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-κB and COX-2. Activation of NF-κB and expression of COX-2 were coincident with neutrophil flattening and adherence to endothelium and infiltration into the intimal space.ConclusionThese data demonstrate activation of NF-κB 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, TNFα 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.