The liver and the hematolymphoid system: I. The regulation of nylon-passed spleen cell proliferation by active factors released from syngeneic nonparenchymal liver cells.

Nylon-passed spleen cells were found to proliferate when cultured with syngeneic nonparenchymal adherent liver cells and their culture supernatants. The supernatants contained IL-1, IL-6, GM-CSF, and IFN (alpha + beta) activities but not IL-2 and IL-3 activities. The IFN level was higher in early culture sup (2-24 hr) than in later culture sup (48-72 hr). Proliferation was greatly increased by anti-IFN (alpha + beta) serum in the spleen cells cultured in the earlier sup. This antiserum increased the spleen cell proliferation only slightly in the later culture sup. This suggests that nonparenchymal liver cells produce two factors, one having a suppressor, and the other an enhancer action, with IFN being one of the suppressor factors. With culture time, DNA synthesis of spleen cells increased and IL-2 and IL-3 activities were generated in the culture sup. Cells proliferated during culture were found to be morphologically lymphocytes, granulocytes, and macrophages. The mechanisms by which nonparenchymal liver cells regulate the hematolymphoid system are discussed based on our observations.

Adhesive interaction between lymphocytes and sinusoidal liver cells.

Since sinusoidal liver cells directly interact with circulating hemopoietic cells and lymphocytes, Kupffer cells may have the capacity to trap and activate these cells in the liver microcirculation. In order to investigate the adhesion mechanism of Kupffer cells to other lymphoid cells, mouse sinusoidal liver cells were isolated by a collagenase perfusion followed by differential centrifugations. By in vitro adhesion assay of lymphocytes to sinusoidal liver cells and staining of adhered lymphocytes with FITC/peroxidase labeled peanut agglutinin (PNA), the following observations were made: 1) Lymphocytes from various lymphoid organs including the liver itself adhered to Kupffer cells. 2) After an incubation period, DNA synthesis of the adhered lymphocytes increased. 3) A high percentage of the adhered lymphocytes were PNA+ cells. 4) D-Galactose, a PNA specific carbohydrate, inhibited the lymphocyte binding and the total DNA synthesis of the adhered lymphocytes decreased proportionally with their decrease in number. Our results suggest that sinusoidal liver cells may have the ability to trap and to activate PNA+ cells.

The liver as a potential hematolymphoid organ examined from modifications occurring in the systemic and intrahepatic hematolymphoid system during liver regeneration after partial hepatectomy.

In order to investigate whether or not the adult murine liver can function as one of the hematolymphoid organs, we studied the alteration of cellular characteristics in the systemic and intrahepatic hematolymphoid systems during liver regeneration after partial hepatectomy. Liver regeneration affects the systemic hematolymphoid system, as can been seen from the transient increase in colony forming unit in culture (CFU-C) frequency observed in the bone marrow at 20 hr and its gradual increase in the spleen up to the 6th day after partial hepatectomy. CFU-C were found not only in peripheral blood lymphocyte-rich fraction (PBL), but also in intrahepatic lymphocyte-rich fraction (IHL) of the normal adult liver. CFU-C frequency showed a weak increase in PBL and a dramatic increase, up to the 6th post-hepatectomy day, in IHL subfraction cells, forming a very strong liver association. Colonies, which were generated from IHL in a fibrin clot culture system, were mainly composed of granulocytes, macrophages and mast cells. Wheat germ agglutinin (WGA) positive cells too were detected in IHL and found to increase after partial hepatectomy. IHL of the normal liver were proliferated not only by IL-3 and GM-CSF but also by IL-2. The proliferative responses of IHL to these cytokines were further augmented on day 6 after partial hepatectomy. Similar results were obtained in peripheral blood and splenic lymphocyte-rich fractions. These observations, therefore, suggest that the adult murine liver has hematolymphoid cells as its component and has the function of a hematolymphoid organ closely associated with the systemic hematolymphoid system.