Reproductive condition and the low-dose endotoxin-induced inflammatory response in rats. Glomerular influx of inflammatory cells and expression of adhesion molecules.
These experiments were designed to study the increased sensitivity of pregnant rats to endotoxin. Pregnant (Pr), cyclic (C), and progesterone (P)-treated pseudopregnant rats with or without a decidualized uterus (PSP and DEC rats, respectively) received infusions of an ultra-low dose of endotoxin (1.0 microg/kg BW) and were killed 3 days later. Pr, PSP, and DEC rats were infused on Day 14, C rats on diestrus. Endotoxin-infused rats were compared with saline-infused rats in the same reproductive conditions. The inflammatory reaction of the glomeruli of the kidneys was studied by immunohistochemical methods using 4-microm cryostat sections stained with specific monoclonal antibodies against neutrophils (polymorphonuclear cells, PMNs) and monocytes (MOs), and against the adhesion molecules ICAM-1 and VCAM-1 on the endothelium, and LFA-1, MAC-1, and VLA-4 on the leukocytes. Endotoxin infusion increased glomerular PMN and MO number in Pr, PSP, and DEC rats, all of which have elevated P levels, but not in C rats, which do not. The endotoxin-induced expression of adhesion molecules, associated with this influx of inflammatory cells, varied with the reproductive condition. In C rats there was no increased adhesion molecule expression after endotoxin treatment, in Pr rats there was increased expression of both the combinations ICAM-1/LFA-1 and VCAM-1/VLA-4. DEC rats did not express either of these combinations (although there was expression of ICAM-1); PSP rats expressed the combination ICAM-1/MAC-1. Adhesion molecule expression thus seems to be regulated by ovarian (e.g., P) and placental factors (e.g., of trophoblastic and decidual origin). Because the different combinations of adhesion molecules in the various reproductive conditions after exposure to endotoxin led to more or less the same leukocyte influx under these conditions, the increased sensitivity to endotoxin of pregnant individuals cannot be reduced to differences in leukocyte influx into the glomeruli.
Faas
M M
MM
Department of Obstetrics and Gynaecology, University of Groningen, The Netherlands.
Bakker
W W
WW
Valkhof
N
N
van der Horst
M C
MC
Schuiling
G A
GA
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D004731:Endotoxins / Q000633:toxicity*; D004971:Estrus / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D011555:Pseudopregnancy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D004731:Endotoxins; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011374:Progesterone