Poly-2-Vinylpyridine N-Oxide Reverses the Immunosuppressive Effects of Silica and Carrageenan

Rios, Angelyn; Simmons, Richard L.

doi:10.1097/00007890-197203000-00026

Cited by 33 publications

(15 citation statements)

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“…These two opposing interpretations are each reasonably consistent with most of the present findings. For example, the reversal of the tumor-enhancing effect exerted by silica and carrageenan by the lysosome stabilizer PVNO, a compound that effectively reduces or prevents the toxic, fibrogenic, and immunosuppressive effects of silica (22,23,25,26,29,54), would be consistent with either mechanism.…”

Section: Discussionmentioning

confidence: 97%

“…Among these, an especially compelling alternative derives from the extraordinary selective susceptibility of macrophages in vitro to the cytotoxicity of silica particles (28,29). Then, also, in vivo administration of silica is known to elicit major alterations in host resistance, e.g., prolonged survival of skin allografts (26,30), abrogation of resistance to bone marrow grafts (25), suppression of established delayed hypersensitivity reactions (31), and depression of resistance to herpes simplex virus (32,33) and yellow fever virus in mice (34). Moreover, silica pretreatment interferes with the establishment of active (30,35,36) and adoptive (37) antitumor immunity and actually induces lymphomatous tumors in Wistar rats (38).…”

Section: Discussionmentioning

confidence: 99%

“…PVNO, a potent macrophage-stabilizing agent, can diminish the fibrogenic and other in vivo effects of silica in animals (22)(23)(24)(25)(26). Therefore, the effect of PVNO pretreatment on the suppressive effects of silica arul carrageenan on tumor resistance was examined.…”

Section: Prevention Of Silica Effects By the Macrophage Stabilizer Pvnomentioning

confidence: 99%

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Promotion of Tumor Growth In Vivo by Antimacrophage Agents 2

Keller

1976

JNCI: Journal of the National Cancer Institute

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ABSTRACT-Various attempts were made to assess the role of the mononuclear phagocyte system in tumor resistance of rats in vivo. The growth of sc inoculated, weakly immunogenic, carcinogen-induced, syngeneic tumor cells was modestly reduced by ip injection and, more impressively, by local injection of peptoneinduced, activated, nonimmune macrophages. A single iv injection of silica particles or carrageenan on the day of sc tumor cell inoculation greatly enhanced tumor growth. When these agents had been given a few days before or after tumor cell inoculation, the tumor-promoting efficiency was distinctly diminished or even cancelled. The enhancing effects of silica and carrageenan on tumor growth were nullified by the macrophage-stabilizing agent, poly-2-vinylpyridine N-oxide. To assess the in vivo consequences of silica administration, various cellular, biochemical, and functional macrophage parameters were determined at different intervals. Results indicated the complexity of events elicited after the mononuclear phagocyte system was damaged, which made the interpretation of such results difficult.-J Natl Cancer Inst 57: 1355-1361,1976. Many in vitro studies indicate that, in addition to the basic role that is assigned to lymphocytes (in tumor resistance), macrophages activated by specific or nonspecific means also contribute to tumor resistance (1). Since presently no direct or effective way exists of depleting the host of macrophages, their function in tumor resistance in vivo remains obscure. However, considerable evidence, admittedly indirect, implies such a capacity for the macrophage (2). For example, in the Nippostrongylus brasiliensis-infected rat, tumor growth can either be suppressed or enhanced, depending on the timing of inoculation of tumor cells in relation to the parasite infection (3). In this (4) and other in vivo model systems (5, 6), suppression of tumor growth seems attributable to AM, and enhancement of tumor growth seems due to a macrophage-inactivating factor arising after a nematode infection (7). Moreover, the use of adjuvants of microbial derivation such as BCG, Corynebacterium parvum, or Listeria monocytogenes has been considerably expanded, and recent evidence attests to intralesional injection of the adjuvant being particularly effective in producing regression of established syngeneic tumors (8)(9)(10)(11). As the responsiveness of tumors to these adjuvants does not parallel their immunogenicity, this effect is now considered more likely to reflect the extent to which tumors are infiltrated by macrophages. Still other observations imply an inverse relationship between the macrophage content of tumors and tumor regression (12) or metastases (13). Despite these distinctive approaches and the expanding magnitude of the effort, no convincing evidence exists that macrophages are directly involved in tumor resistance.The function of macrophages in tumor resistance is explored further in the present study. Various measures known to diminish the functional capacities of macrophages in vi...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Promotion of Tumor Growth In Vivo by Antimacrophage Agents 2

Keller

1976

JNCI: Journal of the National Cancer Institute

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“…Other studies have demonstrated that systemic administration is associated with increased allograft survival. Rios and Simmons (1972) reported that histo-incompatible skin grafts showed extended survival on mice treated i.p. with kappa carrageenen, unless the mice were also treated with poly(2-vinylpyridine Af-oxide) (PVNO), a lysosome-stabilizing agent.…”

Section: Immunological Consequencesmentioning

confidence: 99%

Intestinal uptake and immunological effects of carrageenan—current concepts

Nicklin

Miller

1989

Food Additives and Contaminants

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Carrageenans are a group of high molecular weight sulphated polygalactans which find extensive use in the food industry as thickening, gelling and protein-suspending agents. Although there is no evidence to suggest that the persorption of small amounts of carrageenans across the intestinal barrier poses an acute toxic hazard, they are known to be biologically active in a number of physiological systems and extended oral administration in laboratory animals has been shown to modify both in vivo and in vitro immune competence. Whereas this effect could be attributed to carrageenan having a selective toxic effect on antigen-processing macrophages, additional studies suggest that macrophages can also influence immune responses by the timed release of immunoregulatory mediators. Evidence in support of this comes from in vitro studies which demonstrate that carrageenan-treated macrophages can, depending on conditions and time of administration, release either stimulatory or inhibitory factors. The former is known to be the immunostimulatory agent interleukin 1 (IL-1). The inhibitory factor, which is produced at an early stage following exposure to non-toxic doses of carrageenans, has yet to be formally identified but it is believed to be a prostaglandin because of its specific mode of action and short biological half-life. At present it is impossible to relate these studies to the human situation. Although it is established that carrageenans can cross the intestinal barrier of experimental animals, there is no evidence to suggest that the limited uptake that may occur in man in any way interferes with normal immune competence. Nevertheless, increased exposure may occur in the neonate during weaning, and adults and children following allergic reactions and episodes of gastrointestinal disease. Further studies under such conditions now seem warranted in order to elucidate the possible immunological consequences which may be associated with enhanced uptake of carrageenans in vulnerable groups.

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“…and efferent (cytotoxic) activities of these ceils [2,17,23]. There is no evidence that silica directly affects lymphocytes detrimentally, and its in vivo effects can be reversed by the lysosome-stabilizing agent poly-2-vinylpyridine N-oxide (PVNO) [25]. Powdered quartz particle size 5 ~tm) was suspended in phosphate-buffered saline (PBS) at 10 mg/ml and autoclaved.…”

Section: Selective Ablation Of Mononuclear Phagocyte Functionmentioning

confidence: 99%