LATE EFFECTS OF ENDOTOXIN ON THE ACCUMULATION AND FUNCTION OF MONOCYTES IN RABBIT LUNGS

Recent studies from our laboratory show that the lung contains a marginated pool of monocytes. The present study was designed to investigate monocyte accumulation in this pool 4 to 28 h after a single dose of endotoxin when the endotoxin had disappeared from the circulation. This was accomplished by administering a single intravenous dose of endotoxin (Escherichia coli, 50-mu-g/rabbit) to unanesthetized animals (n = 6) and saline to controls (n = 5) at time 0. Four hours after this dose of endotoxin, In-111-monocytes (93.5% pure) isolated from donors were injected intravenously, and, at 27 h, the rabbits were anesthetized and colloidal carbon (CC, 1 ml/kg body weight) was injected intraarterially to provide a phagocytic stimulus. The animals were sacrificed at 28 h, and the lungs were fixed in situ with glutaraldehyde. The data show that lungs from the endotoxin-treated rabbits contained 4-8 times more In-111-monocytes than controls, that 92% of these radiolabeled monocytes were in the alveolar capillaries, and that 72% of these labeled cells had phagocytosed CC. The histologic studies of unlabeled cells confirmed that this endotoxin treatment caused a 3-5-fold increase in unlabeled mononuclear cells and neutrophils (PMN) in the microvasculature and that many of the unlabeled monocytes in the endotoxin-treated group had also phagocytosed colloidal carbon. The behavior of the donor monocytes injected after the endotoxin had time to disappear from the circulation suggests that they accumulate in the lung in response to the indirect effects of endotoxin on endothelial cells.