TY - JOUR
T1 - Use of ricin a-chain to selectively deplete Kupffer cells
AU - Zenilman, Michael E.
AU - Fiani, Maria
AU - Stahl, Philip
AU - Brunt, Elizabeth
AU - Flye, M. Wayne
PY - 1988/7
Y1 - 1988/7
N2 - We used the A-chain of the toxin ricin (RTA) as a toxin specific to Kupffer cells in mice. RTA is specifically taken up by the mannose receptor present exclusively in macrophages. Kupffer cells were quantitated by shifts in β-glucuronidase clearance and microscopic counts of cells which phagocytosed India ink. When compared to saline controls, 20 mg/kg of RTA intraperitoneally (divided over 4 days) or intraportally (single doses) significantly prolonged the t 1 2 half-life of β-glucuronidase by 270 ± 37 and 210 ± 8%, respectively. Kupffer cell numbers were significantly decreased by 27 ± 8 and 33 ± 16%. This effect persisted for at least 3 days after toxin administration. Despite effects on Kupffer cell number, minimal histological damage to liver, spleen, lung, and heart was noted. Higher doses of RTA or doses potentiated by ureteral ligation to prevent renal clearance resulted in prohibitive mortalities and histologic liver damage. Doses of Hura crepitans inhibitor, a toxin similar to RTA but not mannose-receptor specific, did not affect Kupffer cell numbers. We conclude that RTA given both intraperitoneally and intraportally at low doses is toxic specifically to Kupffer cells. Kupffer cell numbers can be indirectly measured by β-glucuronidase clearance.
AB - We used the A-chain of the toxin ricin (RTA) as a toxin specific to Kupffer cells in mice. RTA is specifically taken up by the mannose receptor present exclusively in macrophages. Kupffer cells were quantitated by shifts in β-glucuronidase clearance and microscopic counts of cells which phagocytosed India ink. When compared to saline controls, 20 mg/kg of RTA intraperitoneally (divided over 4 days) or intraportally (single doses) significantly prolonged the t 1 2 half-life of β-glucuronidase by 270 ± 37 and 210 ± 8%, respectively. Kupffer cell numbers were significantly decreased by 27 ± 8 and 33 ± 16%. This effect persisted for at least 3 days after toxin administration. Despite effects on Kupffer cell number, minimal histological damage to liver, spleen, lung, and heart was noted. Higher doses of RTA or doses potentiated by ureteral ligation to prevent renal clearance resulted in prohibitive mortalities and histologic liver damage. Doses of Hura crepitans inhibitor, a toxin similar to RTA but not mannose-receptor specific, did not affect Kupffer cell numbers. We conclude that RTA given both intraperitoneally and intraportally at low doses is toxic specifically to Kupffer cells. Kupffer cell numbers can be indirectly measured by β-glucuronidase clearance.
UR - http://www.scopus.com/inward/record.url?scp=0023693057&partnerID=8YFLogxK
U2 - 10.1016/0022-4804(88)90025-X
DO - 10.1016/0022-4804(88)90025-X
M3 - Article
C2 - 3392996
AN - SCOPUS:0023693057
SN - 0022-4804
VL - 45
SP - 82
EP - 89
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -