Implication of B lymphocytes in endotoxin-induced hepatic injury after partial hepatectomy in rats

Lymphocyte population constitutes major defense mechanism against endotoxemia, but the role of B lymphocytes in endotoxin-induced hepatic injury after hepatectomy is not clear.

We used lymphopenic (L(-)) rats by single administration of anti-rat lymphocyte serum, nu/nu athymic (T(-)) rats, B cell-ablated (B(-))rats by intermittent injection of anti-immunoglobulin (Ig) micro-chain from birth, and their vehicle controls. These animals were subjected to two-thirds hepatectomy with subsequent intravenous lipopolysaccharides (LPS, 1.5 mg/kg) administration. The survival rate, plasma alanine transaminase (ALT), tumor necrosis factor-alpha (TNF-alpha) and IgM levels, and total hemolytic activity (CH50) were determined. Hepatic tissue deposition of IgM or C3 was assessed with immunohistochemistry.

The 24-h survival rate in control animals was 20%, whereas those in L(-), T(-), and B (-) animals were 80, 0, and 100%, respectively. Lymphocyte-sufficient control (L(+)) and B cell-sufficient control (B(+)) animals showed a rapid elevation of plasma TNF-alpha levels 1 h after the challenge, followed by an increase in plasma ALT levels. In B(+) group, plasma IgM levels were increased and CH50 activities were decreased 4 h after LPS injection with significant difference compared to those at time 0. Liver histology showed massive hepatic necrosis with a dense accumulation of IgM and C3 deposits 4 h after LPS administration. B cell ablation significantly ameliorated plasma ALT, IgM, and CH50 levels, showing less histological liver damage.

B lymphocytes susceptible to LPS might be implicated in the development of endotoxin-induced hepatic injury after partial hepatectomy.