interleukin-8 and Placenta-Diseases

We have shown that fetal plasma from pregnancies with placental vascular disease that were identified by an abnormal umbilical artery Doppler study causes endothelial cell activation. We investigated the hypothesis that this would be associated with endothelial cell production of cytokines and their natural regulators, the suppressor of cytokine signaling family. Activation of suppressor of cytokine signaling at the time of cytokine release confirms the fact that cytokine production is occurring in a stimulated cell.. Aliquots from a common culture of human umbilical vein endothelial cells were incubated with fetal plasma from normal pregnancy (n = 29 pregnancies), from umbilical placental vascular disease defined by abnormal umbilical artery Doppler waveforms (n = 38 pregnancies), and from preeclampsia with normal umbilical artery Doppler scans (n = 10 pregnancies). The expression of messenger RNA for the cytokines interleukin-6 and interleukin-8 and the members of suppressor of cytokine signaling family (cytokine-inducible SH2-containing protein, suppressor of cytokine signaling 1, 2, and 3) were assessed by reverse transcriptase-polymerase chain reaction.. Endothelial cell expression of interleukin-6 messenger RNA (1.94 +/- 0.24 vs 1.31 +/- 0.16) and interleukin-8 messenger RNA (2.62 +/- 0.33 vs 1.64 +/- 0.22) were enhanced in response to incubation with fetal plasma from placental vascular disease in comparison to incubation with fetal plasma from normal pregnancy. The messenger RNA expression of suppressor of cytokine signaling-2 (2.03 +/- 0.23 vs 1.37 +/- 0.16) was up-regulated significantly in placental vascular disease. Differences for cytokine-inducible SH2-containing protein, suppressor of cytokine signaling-1, and suppressor of cytokine signaling-3 were not significant. The expression of cytokines and the suppressor of cytokine signaling family did not differ from normal in the group with maternal preeclampsia and a normal umbilical study. Interestingly, in the umbilical placental vascular disease group, the results were similar in the subgroups, with or without preeclampsia in the mother.. We have shown that factors that cause endothelial cell injury are present in the fetal circulation in umbilical placental vascular disease. This study is the first report of cytokine production and release and activation of the suppressor of cytokine signaling family by endothelial cells in response to fetal plasma in placental vascular disease. The role of all members of the suppressor of cytokine signaling family in this process must be investigated further. The fact that both the agonist (cytokines) and the antagonist (suppressor of cytokine signaling-2) are produced points to a significant role of endothelial cells in this disease.

Topics: Carrier Proteins; Cytokines; DNA-Binding Proteins; Endothelium, Vascular; Female; Fetal Blood; Humans; Interleukin-6; Interleukin-8; Intracellular Signaling Peptides and Proteins; Placenta Diseases; Pregnancy; Pregnancy Outcome; Protein Biosynthesis; Proteins; Repressor Proteins; RNA, Messenger; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Trans-Activators; Transcription Factors; Umbilical Cord

It is unclear why some cows fail to expel the placenta following calving. One theory suggests the fetal placenta must be recognized as "foreign" tissue and rejected by the immune system after parturition to cause expulsion of the placenta. We hypothesized that impaired neutrophil function causes retained placenta (RP). We examined the ability of neutrophils to recognize fetal cotyledon tissue as assessed by a chemotaxis assay, which utilized a placental homogenate obtained from a spontaneously expelled placenta as the chemoattractant. Neutrophil killing ability was also estimated by determining myeloperoxidase activity in isolated neutrophils. Blood samples were obtained from 142 periparturient dairy cattle in two herds. Twenty cattle developed RP (14.1%). Neutrophils isolated from blood of cows with RP had significantly lower neutrophil function in both assays before calving, and this impaired function lasted for 1 to 2 wk after parturition. The addition of antibody directed against interleukin-8 (IL-8) to the cotyledon preparation used as a chemoattractant inhibited chemotaxis by 41%, suggesting that one of the chemoattractants present in the cotyledon at parturition is IL-8. At calving, plasma IL-8 concentration was lower in RP cows (51 +/- 12 pg/ml) than in cows expelling the placenta normally (134 +/- 11 pg/ml). From these data, we suggest that neutrophil function is a determining factor for the development of RP in dairy cattle. Also, depressed production of IL-8 may be a factor affecting neutrophil function in cows developing RP.

Topics: Animals; Cattle; Cattle Diseases; Chemotaxis, Leukocyte; Female; Interleukin-8; Neutrophils; Placenta Diseases; Placenta, Retained; Pregnancy; Pregnancy, Animal; Time Factors