Macrophage regulation of DNA synthesis in lymphoid cells: Effects of a soluble factor from macrophages

Waldman, Stephen R.; Gottlieb, Allan

doi:10.1016/0008-8749(73)90175-5

Cited by 114 publications

(30 citation statements)

References 19 publications

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“…MfID was found to be heat-stable and non-dialysable (Table 2). Some investigators have described the soluble factors suppressing cellular DNA synthesis which are released by macrophages of "normal" rats (Waldman and Gottlieb 1973;Reed and Lucas 1975) or mice (Calderon et al 1974;Lejeune 1976). These are consistent with our factor on thermostability.…”

Section: Discussionsupporting

confidence: 88%

“…But the feature of MfID against dialysis differed from the factors of mouse origin which are dialyzable. Especially, it is in confusion, still to be characterized, that there is a diametrical difference between MfID and MDF (Waldman and Gottlieb 1973), in spite of the fact that both are of rat origin.…”

Section: Discussionmentioning

confidence: 99%

“…However, the role of macrophages in these areas has not been well defined. Recently, macrophages have been shown to inhibit DNA synthesis in lymphocytes (Harris 1965; Parkhouse and Dutton 1966; Yoshinaga et al 1972;Waldman and Gottlieb 1973;Miller and Mishell 1975;Baird and Kaplan 1977) and other cells (Keller 1973;Krahenbuhl and Remington 1974;Reed and Lucas 1975;Lejeune 1976), irrespective of whether they are derived from normal (Waldman and Gottlieb 1973;Miller and Mishell 1975;Reed and Lucas 1975;Lejeune 1976;Baird and Kaplan 1977) or activated (Keller 1973; Krahenbuhl and Remington 1974;Baird and Kaplan 1977) animals. These findings suggest that one vital function of macrophages is to regulate cellular proliferation and differentiation.…”

mentioning

confidence: 99%

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Inhibition of Cellular DNA Synthesis by Rat Peritoneal Macrophages

Toh¹,

Sato²,

Kikuchi³

1977

Tohoku J. Exp. Med.

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The DNA synthesis in syngeneie, allogeneic and xenogeneic cells was inhibited by peritoneal macrophages of normal WKA rats. This inhibitory effect of macro phages was found to be mediated by a soluble factor (MfID) released into a culture medium from macrophages which was heat-stable and non-dialyzable. The MfID was also responsible for the inhibition of lymphocyte DNA synthesis by MIX reaction.The action of MfID was indicated to suppress rather than to kill cell growth.It was interpreted that the inhibitory effect of macrophages on cellular DNA synthesis is their inherent property and macrophages may play the role of regulating the proliferation of lymphocytes and other cells. rat peritoneal macrophage; macrophage soluble factor; DNA synthesisIt is well known that macrophages are essential cells at the site of inflamma tion, wound repair, graft rejection, etc. However, the role of macrophages in these areas has not been well defined. Recently, macrophages have been shown to inhibit DNA synthesis in lymphocytes (Harris

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Inhibition of Cellular DNA Synthesis by Rat Peritoneal Macrophages

Toh¹,

Sato²,

Kikuchi³

1977

Tohoku J. Exp. Med.

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“…Since supernatants from mononuclear cells stimulated with HSV antigen were ineffective in promoting T cell proliferation, the mechanism by which the monocyte enhances transformation probably requires cell-to-cell contact rather than soluble mediators (37,38). Soluble antigens can be concentrated by monocytes to give a more potent stimulus to lymphocytes (39).…”

Section: Effect Of Recurrent Infection On Lymphocytementioning

confidence: 99%

Role of T lymphocytes in cellular immune responses during herpes simplex virus infection in humans.

Rasmussen¹,

Merigan²

1978

Proc. Natl. Acad. Sci. U.S.A.

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Lymphocyte blast transformation and interferon production in mononuclear cell cultures prepared on Ficoll-Hypaque gradients from individuals with herpes simplex virus-I infection were enhanced by a disease recurrence. Responses to both herpes simplex virus-2 and phytohemagglutinin were unaltered. Transformation to herpes simplex virus-i antigen was adversely affected by depleting either thymus-derived (T) lymphocytes or bone marrow-derived (B) lymphocytes to- In humans, cellular immunity to HSV has been studied by using different in vitro variables, most commonly, lymphocyte transformation. The significance of lymphocyte transformation as a correlate of susceptibility to recurrent HSV infection is not established. Defects in transformation to HSV antigen associated with acute disease have been detected by some investigators (6), but not by others (7-11). Defects in lymphokine production in vitro, for example, in migration inhibiting factor and interferon production have been reported during acute HSV infection (7,12). In cardiac transplant recipients, low responses of lymphocyte interferon production and transformation to HSV antigen are associated with both severe and prolonged HSV infection (13).It is important to measure responses of thymus-derived (T) lymphocytes to specific antigens in cellular immune reactions. Mitogens. Lyophilized phytohemagglutinin-P (PHA) (Difco, Detroit, MI) was reconstituted in 5 ml of phosphate buffered saline and diluted 1:30. Pokeweed mitogen (PWM) (Gibco, Grand Island, NY) was reconstituted in 10 ml of the buffered saline and diluted 1:60. Mononuclear Cell Cultures. The microculture assay for lymphocyte transformation and interferon production from cells separated on Ficoll/Hypaque (FH) gradients has been described (22). T lymphocytes were purified on nylon fiber columns (23). The eluate was centrifuged on a FH gradient. T lymphocytes so prepared gave at least 60% rosette formation with papain-treated sheep erythrocytes (24), and at least 95% were killed by anti-human T lymphocyte sera (25).Bone marrow-derived (B) lymphocyte-enriched populations were obtained by incubating 5 X 106 mononuclear cells per ml with 0.5% papain-treated sheep erythrocytes in 50% fetal calf serum for 15 min at room temperature. The mixture was centrifuged at 200 X g for 5 min and held for 1.5 hr at room temperature. After gently resuspending the cell pellet and centrifuging at 400 X g for 30 min on a FH gradient, the nonrosetted cells at the interface of the FH and medium had residual rosette-forming cells of less than 5% and, for most experiments, less than 1%. Of the nonrosetted cells, 10-70% had surface immunoglobulins and 10-40% were monocytes.For monocyte depletion, leukocytes from dextran-sedimented, heparinized blood were centrifuged at 200 X g, resuspended in 30 ml McCoy's 5A medium, and incubated for

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“…Waldman & Gottlieb (1973) have presented evidence that macrophages are able to secrete a factor that apparently inhibits mitosis, and Badger et al (1973) have described a factor with similar effects secreted by mitogen-stimulated lymphocytes. Calderon et al (1974) and Stadecker et al (1977) The fact that significant in vivo and in vitro anti-tumour activities were always paralleled by the generation of nonspecific suppressor-cell activity in our system poses the question of the involvement of the latter cells in these mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Possible role of macrophage-like suppressor cells in the anti-tumour activity of BCG

Castes¹,

Lynch²,

Lespinats³

et al. 1981

Br J Cancer

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Summary.-The i.v. injection of high doses (3 mg) of BCG into C3H mice bearing a transplantable 3-methylcholanthrene-induced fibrosarcoma caused the regression of a significant proportion. This effect was most evident when the BCG was injected on the day of the graft, or 7 days later. The injection of this agent either 14 days before the graft, or in low doses (0.1 or 0 5 mg), or directly into the tumour (i.t.) only prolonged the survival of the animals. Spleen cells from systemic high-dose BCGtreated mice were found to exert a strong nonspecific cytostatic effect in vitro that was not an artefact of the test conditions, and was not expressed by cells from lowdose animals. The cytostatic effect was shown to be caused by cells with the characteristics of macrophages, i.e. they were strongly adherent, unaffected by treatment with anti-Thy 1.2 + C', radioresistant but heat-sensitive, and were detected in BCG-treated "B" mice.The spleens of high-dose BCG-treated mice also contained suppressor cells that were capable of inhibiting the in vitro reactivity of normal T cells to PHA. Like the cytostatic effect, this suppressor activity was not detected in low-dose mice, and the cells responsible had the properties of macrophages; the effect was lost after the removal of adherent cells by sequential exposure to plastic and colloidal iron, but was conserved after treatment with anti-Thy 1.2 + C'. T-cell-deprived animals, such as "B" or nude mice, also developed suppressor-cell activity when treated with systemic high-dose BCG.Close parallels became evident between the in vivo anti-tumour activity of BCG, the in vitro cytostatic effect, and the suppressor-cell activity. We here discuss the possible role of suppressor cells in the mechanism of action of this agent.

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Macrophage regulation of DNA synthesis in lymphoid cells: Effects of a soluble factor from macrophages

Cited by 114 publications

References 19 publications

Inhibition of Cellular DNA Synthesis by Rat Peritoneal Macrophages

Inhibition of Cellular DNA Synthesis by Rat Peritoneal Macrophages

Role of T lymphocytes in cellular immune responses during herpes simplex virus infection in humans.

Possible role of macrophage-like suppressor cells in the anti-tumour activity of BCG

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