Proliferative Response of the Spleen and Liver to Hemolysis

Abstract

Combined chemical and autoradiographic studies in rats injected with tritiated thymidine indicate that acute red cell sequestration stimulates reticuloendothelial (RE) proliferation. In the spleen DNA synthesis is most markedly stimulated in the marginal zone which is also the initial site of red cell sequestration. This proliferative response involves several division steps and eventuates in a colonization of the red pulp with increased numbers of all cell lines native to the spleen. In both spleen and liver there occurs also a generalized stimulation of division in the macrophages and littoral cells which involves only 1 or 2 division steps. Chronic compensated hemolytic anemia achieved in rats by injections of phenylhydrazine caused functional overactivity of the RE system, including increased sequestering function and hypergammaglobulinemia. This splenic hyperplasia did not entirely regress after cessation of the injections. In man the splenomegaly of a chronic non-immunological hemolytic anemia, hereditary spherocytosis, was found to involve a marked (average: 8-fold) hyperplasia of all spleen cellular elements. Neither the acute nor chronic proliferative reaction appears to arise from immunological or "toxic" stimuli and the findings support the view that the size of the RE system is a function of its particulate "work load." It is suggested that the cytoproliferative aspects of immune responses may depend upon non-specific, usually particulate stimulation. After prolonged stimulation, hyperplasia of the RES may become partly irreversible.

Erythrocyte Catabolism by Macrophages In Vitro THE EFFECT OF HYDROCORTISONE ON ERYTHROPHAGOCYTOSIS AND ON THE INDUCTION OF HEME OXYGENASE

“…DISCUSSION There is extensive morphologic (23,24) and experimental (10,25) evidence that macrophages and other mononuclear phagocytes possess the capacity to engulf intact or fragmented erythrocytes and to digest them. Erythrophagocytosis by these cells appears to be an important, and perhaps the primary mechanism by which physiologically aged or damaged red blood cells are removed from the circulation (1,(26)(27)(28). This process can be reproduced in vitro, in that in a variety of culture systems isolated macrophages may be observed ingesting and degrading offered erythrocytes that previously had been injured by chemical or physical means (10,29).…”

Red cell survival studies in hereditary spherocytosis

“…The survival of hereditary spherocytes in the circulation is influenced by two major factors, the intrinsic defect in the cell and the interaction of this cell with the spleen. Since splenic hyperplasia involving all cellular elements occurs in hereditary spherocytosis (12), not only will reticuloendothelial activity be altered but also splenic blood flow will be increased. To eliminate any effect of abnormal splenic function or blood flow, the survival curve of hereditary spherocytes was measured in compatible recipients and the ti was taken to reflect the intrinsic hemolytic defect of the cell.…”

A murine recombinant retrovirus containing the src oncogene transforms erythroid precursor cells in vitro.

“…7). Phenylhydrazine treatment induces anemia and elevates the number of erythroid precursors (14). Formation of erythroid bursts occurred with a time course similar to that observed with fetal liver cells, with the maximum number and maximum size of bursts occurring at 7 to 8 days postinfection.…”

“…6). In either case, MRSV-induced bursts were observed on day 4 postinfection, with the maximum being scored after 7 colonies gradually declined due to the lyses of terminally differentiated erythroid cells, and only rare bursts were obtained subsequent to day 14. The extent of hemoglobinization, maximal in the presence of erythropoietin, also reached a peak at days 7 through 9. Similar experiments were performed with fetal liver cells from C57BL/6 mice (Fig.…”