During the course of observations on the cells of mouse spleen that adhere to glass and plastic surfaces, it was clear that this population was quite heterogeneous. In addition to mononuclear phagocytes, granulocytes, and lymphocytes, we noticed a large stellate cell with distinct properties from the former cell types. In this paper, we describe the morphology, quantitation, and tissue distribution of this novel cell as identified in vitro. In following papers, we will further characterize it with respect to its functional properties in vitro, as well as its localization and properties in situ. Materials and MethodsMice.--Outbred NCS mice were maintained at The Rockefeller University. Inbred DBA/2J, C3H, BALB/cJ, C57BL, and C57BL )< DBA/2J strains weIe obtained from the Jackson Laboratory, Bar Harbor, Maine. Mice, homo-and heterozygous at the nude locus, were kindly provided by Dr. P. Wernet of The Rockefeller University.

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SummaryThalidomide selectively inhibits the production of human monocyte tumor necrosis factor a (TNF-a) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 Ag/ml . In contrast, the amount of total protein and individual proteins labeled with [31 S]methionine and expressed on SDS-PAGE are not influenced . The amounts of interleukin 10 (11,1(3), Ilr6, and granulocyte/ macrophage colony-stimulating factor produced by monorytes remain unaltered . The selectivity of this drug may be useful in determining the role of TNF-a in vivo and modulating its toxic effects in a clinical setting.

The origin and turnover of efferent populations of mouse mononuclear phagocytes has been described. Mononuclear phagocytes were defined as mononuclear cells which are able to adhere to glass and phagocytize. In vitro labeling studies with thymidine-3H showed that monocytes in the peripheral blood and peritoneal macrophages do not multiply and can be considered end cells in a normal, steady state situation. However, the mononuclear phagocytes of the bone marrow appear to be rapidly dividing cells. This conclusion was supported by in vivo labeling experiments. A peak of labeled mononuclear phagocytes of the bone marrow was found 24 hr after a pulse of thymidine-3H. This was followed, 24 hr later, by a peak of labeled monocytes in the peripheral blood. From these experiments it was concluded that the rapidly dividing mononuclear phagocytes of the bone marrow, called promonocytes, are the progenitor cells of the monocytes. Labeling studies after splenectomy and after X-irradiation excluded other organs as a major source of the monocytes. Peak labeling of both the blood monocyte and peritoneal macrophages occurred at the same time. A rapid entry of monocytes from the blood into the peritoneal cavity was observed, after a sterile inflammation was evoked by an injection of newborn calf serum. These data have led to the conclusion that monocytes give rise to peritoneal macrophages. No indications have been obtained that mononuclear phagocytes originate from lymphocytes. In the normal steady state the monocytes leave the circulation by a random process, with a half-time of 22 hr. The average blood transit time of the monocytes has been calculated to be 32 hr. The turnover rate of peritoneal macrophages was low and estimated at about 0.1% per hour. On the basis of these studies the life history of mouse mononuclear phagocytes was formulated to be: promonocytes in the bone marrow, → monocytes in the peripheral blood, → macrophages in the tissue.