The role of Kupffer cells and regulation of neutrophil migration into the liver by macrophage inflammatory protein-2 in primary listeriosis in mice

Depletion of mouse Kupffer cells and splenic macrophages following intraven ous administration of liposome-entrapped clodronate severely reduced host r esistance to primary infection with Listeria monocytogenes, Infection of cl odronate-treated mice with a sublethal dose of L. monocytogenes resulted in death of the mice within 3 days. The macrophage depletion resulted in mark ed increases in bacterial growth in the liver and spleen, but not in other tissues. The proliferation of L. monocytogenes was observed in a large numb er of hepatocytes that underwent apoptosis. Infiltration of neutrophils in the liver and rapid formation of microabscesses were observed in the contro l mice after L. monocytogenes infection. However, there was less accumulati on of neutrophils in the liver of Kupffer cell-depleted mice than in the co ntrol mice, Expression of macrophage inflammatory protein-2 (MIP-2) was enh anced in the livers of both the control and Kupffer cell-depleted mice afte r L. monocytogenes infection. MIP-2 was also induced in a murine hepatocyte cell line following L. monocytogenes infection. The administration of neut ralizing anti-interleukin-8 receptor homolog antibody severely abrogated ne utrophil infiltration into the Listeria-infected mouse liver, Anti-MIP-P an tibody moderately reduced neutrophil infiltration and microabscess formatio n in the liver. These findings indicate that Kupffer cells protect hepatocy tes from L. monocytogenes infection and the resultant apoptosis. Moreover, MIP-2 and its related molecules produced by the infected hepatocytes regula te neutrophil infiltration and microabscess formation in primary listeriosi s.