The effect of kupffer cell stimulation or depression on the development of liver metastases in the rat

Abstract

Tumour cells from a squamous carcinoma (approximately 2.5 X 10(5)) were injected intraportally into a syngeneic strain of rats to produce liver metastases 14 days later. Kupffer cells were stimulated by Corynebacterium parvum (7 mg or 1 mg i.v.) and zymosan (10 mg intraportally). Kupffer cell activity was depressed by the administration of silica, gadolinium chloride or human red cells. The animals in each group were sacrificed at 14 days, the livers removed and the number of visible surface metastases counted and compared. (Mann-Whitney U-test). Kupffer cell stimulation significantly reduced the number of surface liver metastases in all animals (P 0.0048). In contrast depression of Kupffer cell activity significantly increased the number of metastases in all animals (P 0.0045), suggesting that the activity of these cells has an important effect on the development of liver metastases.

The renin angiotensin system regulates Kupffer cells in colorectal liver metastases

“…35,36 Current research attributes a predominantly anti-tumor phenotype to KCs during the early stages of tumor establishment. [37][38][39] Our study in agreement with these reports indicates early KC depletion to have a tumor stimulatory effect. The anti-tumor activity of KCs at this early stage is attributed to their phagocytic properties, 40 while captopril exerts its anti-tumor effect through inhibition of angiogenesis, tumor proliferation and reduction in inflammation.…”

Prevention of hepatic tumor metastases in rats with herpes viral vaccines and gamma-interferon.

“…Perioperative immunostimulation has been examined as a means of decreasing tumor (28,29). In the current study, we employed ␥IFN, a multifunctional protein with a wide range of immunostimulatory effects, for immunoactivation (26,30).…”

Gadolinium Blocks Rat Kupffer Cell Calcium Channels: Relevance to Calcium–Dependent Prostaglandin E2 Synthesis and Septic Mortality

“…8,9,16 Further evidence implicating KC in septic shock and mortality is the observation that the systemic administration of the lanthanide ion, gadolinium chloride (GD), inhibits in vivo phagocytosis by KC, 17 and reduces the mortality of sepsis 18 and anaphylaxis. 19 More recently, GD has been shown to impair KC antigen presentation, 2 enhance intrahepatic metastases, 20 and alter KC phenotype. 21,22 GD is a member of the trivalent cations of the lanthanide series (La, Ce, Pr, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) that exhibits properties similar to that of calcium in biological systems, presumably by virtue of its comparable ionic radius.…”