Glomerular inflammation in pregnant rats after infusion of low dose endotoxin. An immunohistological study in experimental pre-eclampsia.
Increased endotoxin sensitivity during pregnancy occurs in many animals, including rats. The mechanism of this phenomenon is not understood. In the present study it was investigated whether this increased sensitivity is reflected by an altered inflammatory pattern. Inflammatory cell influx, the O2(-)-producing potential of these cells, and expression of adhesion molecules was studied in the glomeruli of pregnant and cyclic rats at various intervals after low dose endotoxin infusion. Kidney sections were stained for monocytes and adhesion molecules (ICAM-1, VCAM-1, LFA-1, and VLA-4) using monoclonals, while potentially O2(-)-producing neutrophils (ie, activated neutrophils) were quantified using immunohistochemical methods. The results show early glomerular influx of activated neutrophils, maximally 4 hours after endotoxin. Both absolute neutrophil counts and relative numbers of activated neutrophils were significantly increased in pregnant versus cyclic rats. In contrast to cyclic rats, showing transient monocyte influx, in pregnant endotoxin-treated rats monocyte influx reaches a maximum at t = 168 hours. These cell kinetics were paralleled by expression of the various adhesion molecules. It was concluded that pregnancy profoundly influences not only the inflammation kinetics after endotoxin, but also the violence of the reaction, reflected by activated neutrophils. This altered glomerular inflammatory pattern may help to explain why low dose endotoxin infusion induces pre-eclamptic-like symptoms (such as an intraglomerular prothrombotic microenvironment and proteinuria) exclusively in the pregnant rat.
D000818:Animals; D015815:Cell Adhesion Molecules / Q000187:drug effects; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology*; D007958:Leukocyte Count; D008264:Macrophages / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D011225:Pre-Eclampsia / Q000139:chemically induced / Q000473:pathology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D015815:Cell Adhesion Molecules; D004731:Endotoxins