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 progesteron e (P)-treated pseudopregnant rats with or without a decidualized uteru s (PSP and DEC rats, respectively) received infusions of an ultra-low dose of endotoxin (1.0 mu g/kg BW) and were killed 3 days later. Pr, P SP, and DEC rats were infused on Day 14, C rats on diestrus. Endotoxin -infused rats were compared with saline-infused rats in the same repro ductive conditions. The inflammatory reaction of the glomeruli of the kidneys was studied by immunohistochemical methods using 4-mu m cryost at sections stained with specific monoclonal antibodies against neutro phils (polymorphonuclear cells, PMNs) and monocytes (Mempty sets), and against the adhesion molecules ICAM-1 and VCAM-1 on the endothelium, and LEA-I, MAC-1, and VLA-4 on the leukocytes. Endotoxin infusion incr eased glomerular PMN and Mempty set number in Pr, PSP, and DEC rats, a ll of which have elevated P levels, but not in C rats, which do not Th e endotoxin-induced expression of adhesion molecules, associated with this influx of inflammatory cells, varied with the reproductive condit ion. In C rats there was no increased adhesion molecule expression aft er endotoxin treatment, in Pr rats there was increased expression of b oth the combinations ICAM-1/LFA-1 and VCAM-1/VLA-4. DEC rats did not e xpress either of these combinations (although there was expression of ICAM-1); PSP rats expressed the combination ICAM-1/MAC-1. Adhesion mol ecule expression thus seems to be regulated by ovarian (e.g., P) and p lacental factors (e.g., of trophoblastic and decidual origin). Because the different combinations of adhesion molecules in the various repro ductive conditions after exposure to endotoxin led to more or less the same leukocyte influx under these conditions, the increased sensitivi ty to endotoxin of pregnant individuals cannot be reduced to differenc es in leukocyte influx into the glomeruli.