The origin, kinetics, and characteristics of the kupffer cells in the normal steady state

Abstract

Enzymatic digestion with pronase and DNAase was used to isolate Kupffer cells from mouse liver. The characteristics of these cells were found to be similar to those of peritoneal macrophages, except that in the initial suspension the percentage of Kupffer cells with Fc receptors was low, C receptors were absent and the ingestion of opsenized bacteria was very poor, because of the effect of pronase on the cell membrane. After 24 h incubation in vitro all these characteristics return. The in vitro and 1 h-pulse [(3)H]thymidine labeling of the Kupffer cells is low (0.8 and 1 percent, respectively) indicating that in essence these cells do not divide. It was also shown that the small percentage of in vitro labeled Kupffer cells was recently derived from the circulation. After an intravenous injection of zymosan the in vitro labeling index of the Kupffer cells increased 16-fold, but it was proven that these dividing cells were immature mononuclear phagocytes very recently recruited from the bone marrow. The labeling of Kupffer cells aider one or four injections of [(3)H]thymidine reached a peak of 10.4 percent at 48 h or 24.1 percent at 60 h, respectively, indicating that these cells are derived from labeled monocytes. Further evidence for this conclusion was obtained by the absence of an increase of labeled Kupffer cells during treatment with hydrocortisone, which causes a monocytopenia during which no circulating monocytes are available to migrate to the tissues. Labeling studies in animals X-irradiated with hind-limb shielding gave a Kupffer cell labeling index of 5-10 percent of the normal values, which confirms their bone marrow origin. A quantitative study on the production of labeled monocytes in the bone marrow and their transit through the circulation showed that in the normal steady state at least 56.4 percent of the monocytes leaving the circulation become Kupffer cells. Considering the Kupffer cells as kinetically homogeneous this gives a mean turnover time of the total population of Kupffer cells of 21 days.

Origin, Kinetics, and characteristics of pulmonary macrophages in the normal steady state.

“…The present study shows that both PAM and PTM have the characteristics of mononuclear phagocytes similar to those of other macrophages studied in mice in the steady state (15,22). The data from the in vitro and in vivo labeling studies with 3H-thymidine provide conclusive evidence that in the steady state neither PAM nor PTM proliferate in a compartment in the lung but are derived from circulating monocytes, as has been established for murine peritoneal macrophages (18) and Kupffer cells…”

“…The presence of Fc and C3 receptors was detected on glass-adherent cells by the use of SRBC coated with heat-inactivated mouse anti-SRBC serum, and of SRBC coated with the IgM fraction of rabbit anti-SRBC serum and complement from fresh mouse serum, as described elsewhere (15).…”

“…Staphylococcus epidermidis in the presence of NBCIS, as described elsewhere (15). Phagocytosis of sheep erythrocytes (SRBC) coated with antibody with or without complement was studied in the experiments for the detection of Fc receptors and C3 receptors (see below).…”

“…Phagocytosis of sheep erythrocytes (SRBC) coated with antibody with or without complement was studied in the experiments for the detection of Fc receptors and C3 receptors (see below). Pinocytosis of glass-adherent cells was studied with dextran sulphate as described elsewhere (15).…”

Role in Nitric Oxide in Kupffer Cell-Mediated Hepatoma Cell Cytotoxicity In Vitro And Ex Vivo

“…Both reduction of NO synthesis by L-NAME, an inhibitor release of massive amounts of NO in association with activaof NO synthesis and the depletion of Kupffer cells function tion of NO synthesizing enzymes in Kupffer cells. As a result, in liver by GdCl 3 …”