monocyte subpopulations from pre-eclamptic patients are abnormally skewed and exhibit exaggerated responses to toll-like receptor ligands从pre-eclamptic单核细胞亚群患者异常扭曲和夸张的toll样受体配体的反应.pdfVIP

Monocyte Subpopulations from Pre-Eclamptic Patients Are Abnormally Skewed and Exhibit Exaggerated Responses to Toll-Like Receptor Ligands 1 2.¤ 1 . Ebtisam Al-ofi , Seth B. Coffelt , Dilly O. Anumba * 1 Academic Units of Reproductive Developmental Medicine, University of Sheffield Medical School, Sheffield, United Kingdom, 2 Inflammation Tumour Targeting, University of Sheffield Medical School, Sheffield, United Kingdom Abstract The leading cause of pregnancy-associated mortality and morbidity is pre-eclampsia (PE). Although information regarding the etiology of this disease is scant, its pathophysiology is characterized by abnormal placentation, endothelial dysfunction as well as an exaggerated inflammatory response. Clinical evidence also indicates that the abundance of many immune cells at the feto-maternal interface and in the circulation of PE patients is abnormal, when compared with normal pregnant (NP) controls. In addition, the phenotype and function of some of these cells is altered. To further characterize the systemic effects of PE on circulating cells, we analyzed monocytic subpopulations in NP and PE patients by flow cytometry. We found that non-classical CD14lowCD16+ monocytes are significantly increased in women with PE and they display irregular expression of several chemokine receptors and antigen presentation molecules. The most striking phenotypic difference among the cell surface molecules was the marked upregulation of TLR4 expression, where both CD14highCD16+ and CD14lowCD16+ monocytes demonstrated higher levels than their NP counterparts. Stimulation of PE monocytes with TLR ligands resulted in profound secretion of various cytokines in comparison with NP contr