TY - JOUR
T1 - Hepatic versus pulmonary uptake of particles injected into the portal circulation in sheep
T2 - Endotoxin escapes hepatic clearance causing pulmonary inflammation
AU - Decamp, M. M.
AU - Warner, A. E.
AU - Molina, R. M.
AU - Brain, J. D.
PY - 1992
Y1 - 1992
N2 - Removal of circulating particulates (bacteria, cell debris, endotoxin) is accomplished in most species by macrophages resident in the liver and spleen. We have shown that sheep and other species have phagocytic macrophages resident in their pulmonary capillaries. Moreover, these pulmonary intravascular macrophages accomplish the bulk of uptake of injected tracer particles, bacteria, or endotoxin (LPS). Because bacteria or LPS of intestinal origin enter the portal circulation, they would first encounter hepatic mononuclear phagocytes. We sought to determine the extent to which particulates injected into the portal circulation of sheep would be taken up by liver or by lung macrophages. Sheep (four per group) were injected via a mesenteric vein with radiolabeled gold colloid, magnetic iron oxide particles, live Pseudomonas aeruginosa, or 125I E. coli endotoxin. For each, the uptake pattern was determined 1 h after injection. Lung and liver were also fixed to determine the cells responsible for uptake and subsequent inflammatory changes. We found that for circulating gold colloid, iron oxide particles, or bacteria, hepatic uptake predominated, and Kupffer cells were responsible. After hepatic uptake of bacteria, inflammatory changes were confined to the liver. In contrast, nearly 50% of endotoxin escaped hepatic clearance and was subsequently removed by the lungs. We then saw inflammatory changes in both lungs and liver. Thus, hepatic macrophages are active in species with pulmonary intravascular macrophages, partially sparing the lungs from uptake and acute inflammation. Endotoxin, however, may elude hepatic uptake, be sequestered in the lungs, and initiate inflammation there.
AB - Removal of circulating particulates (bacteria, cell debris, endotoxin) is accomplished in most species by macrophages resident in the liver and spleen. We have shown that sheep and other species have phagocytic macrophages resident in their pulmonary capillaries. Moreover, these pulmonary intravascular macrophages accomplish the bulk of uptake of injected tracer particles, bacteria, or endotoxin (LPS). Because bacteria or LPS of intestinal origin enter the portal circulation, they would first encounter hepatic mononuclear phagocytes. We sought to determine the extent to which particulates injected into the portal circulation of sheep would be taken up by liver or by lung macrophages. Sheep (four per group) were injected via a mesenteric vein with radiolabeled gold colloid, magnetic iron oxide particles, live Pseudomonas aeruginosa, or 125I E. coli endotoxin. For each, the uptake pattern was determined 1 h after injection. Lung and liver were also fixed to determine the cells responsible for uptake and subsequent inflammatory changes. We found that for circulating gold colloid, iron oxide particles, or bacteria, hepatic uptake predominated, and Kupffer cells were responsible. After hepatic uptake of bacteria, inflammatory changes were confined to the liver. In contrast, nearly 50% of endotoxin escaped hepatic clearance and was subsequently removed by the lungs. We then saw inflammatory changes in both lungs and liver. Thus, hepatic macrophages are active in species with pulmonary intravascular macrophages, partially sparing the lungs from uptake and acute inflammation. Endotoxin, however, may elude hepatic uptake, be sequestered in the lungs, and initiate inflammation there.
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U2 - 10.1164/ajrccm/146.1.224
DO - 10.1164/ajrccm/146.1.224
M3 - Article
C2 - 1320819
AN - SCOPUS:0026733401
SN - 0003-0805
VL - 146
SP - 224
EP - 231
JO - American Review of Respiratory Disease
JF - American Review of Respiratory Disease
IS - 1
ER -