Production of lymphocyte activating factor in the absence of endogenous pyrogen by rabbit or human leukocytes stimulated by a muramyl dipeptide derivative

Damais, C.; Riveau, Gilles; Parant, M; Gerota, J; Chedid, L

doi:10.1016/0192-0561(82)90020-0

Cited by 76 publications

(25 citation statements)

References 20 publications

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“…Furthermore, these supernatants were submitted to filtration through Ultrogel AcA 54 (LKB). The fraction containing the thymocyte-stimulating activity was identical to that obtained with supernatants of muramyl-dipeptide-triggered monocytes (35). The corresponding molecular weight was around 20,000, as reported for IL-1 (36) (data not shown, to be reported elsewhere).…”

Section: Discussionsupporting

confidence: 57%

Leukemia cell lines can replace monocytes for mitogen-induced T-lymphocyte responses: this accessory function is dependent upon their differentiation stage.

Wakasugi¹,

Harel²,

Dokhélar³

et al. 1983

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

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Highly purified peripheral T.lymphocytes do not proliferate.in response to phytohenagglutinin A or concanavalin A, unless adherent.HLA-DR' monocytes are added as aceessory cells. The accessory function (AF) of monocytes is mediated through the release of interleukin-l (IL-1). We here report that cells from three human leukemic lines-K562, HL-60, and U?937-could exert AF and efficiently-replace monocytes in a 72-hr mitogen-stimulated proliferation assay. This AF was clearly related.to precise maturational4stages of these cells, since the hematopoietic precursor K562. cells spontaneously exerted high AF but lost this property when treated with differentiation inducers 'such as sodium butyrate-or phorbol 12-myristate 13-acetate (PMA). On the other hand, untreated HL-60 and U+937 cells exhibited no spontaneous AF, but theyacquired this function when induced to differentiate either along the granulocytic pathway (dimethyl sulfoxide-treated HL-60 cells) or along the monocytic pathway (PMAtreated HL-60. and U-937 cells). Supernatants-from PMA-triggered K562 or HL-60 cells allowed the proliferative 'response of murine thymocytes to phytohemagglutinin A and'were therefore shown to contain IL-1. Analysis of phenotypical markers showed that AF and IL-I production were not restricted to cells of the monocytic lineage. No HLA-DR antigen could be detected on K562 and HL-60 cells. Thus, the expression of HLA-DR antigens is not required for AF and IL-I production inresponse to mitogens. Human leukemia cell lines could provide usefulsources of human IL-1.

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Section: Discussionsupporting

confidence: 57%

Leukemia cell lines can replace monocytes for mitogen-induced T-lymphocyte responses: this accessory function is dependent upon their differentiation stage.

Wakasugi¹,

Harel²,

Dokhélar³

et al. 1983

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

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“…IL-1 was a supernatant from human monocytes stimulated with MDP (9) and was a kind gift of C. Damais The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.…”

Section: Methodsmentioning

confidence: 99%

Modification of T-cell proliferation and interleukin 2 production in mice infected with Trypanosoma cruzi.

Harel‐Bellan¹,

Joskowicz²,

Fradelizi³

et al. 1983

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

103

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Acute infection of mice with Trypanosoma cruzi results in severe immunodepression and the appearance of autoimmune symptoms. In vitro, concanavalin A-stimulated T cells from spleens of infected animals could neither produce nor respond to interleukin 2. Interleukin 2 production was not restored by addition of exogenous interleukin 1, and proliferative response to concanavalin A was not restored by exogenous interleukin 2. A population of Thy-i-negative cells in the spleen of infected animals was shown to suppress the concanavalin A proliferative response and, to a lesser extent, the production of interteukin 2. These and other symptoms of T. cruzi-infected mice are similar to the immune dysfunction of autoimmune Ipr/lpr mice. These findings are discussed in relationship to the pathology of Chagas disease.Trypanosoma cruzi causes Chagas disease in man. The disease is characterized by a variable acute phase during which trypomastigotes circulate, followed by a lifelong chronic phase in which parasites are not detected in circulation but rather appear to be sequestered in the tissues (1). The parasites persist in the chronically infected individuals in spite of the presence of high levels of circulating anti-T. cruzi antibodies. The mouse has been used as a laboratory model for Chagas disease because injection of parasites gives rise to both acute and chronic infections.Severe perturbations of the host immune system accompany T. cruzi infections in the mouse (1-4). On one hand, autoantibodies directed to various host antigens are induced. On the other hand, severe immunodepression has been reported to occur during the acute phase of the infection, and cellular responses to mitogens, parasite antigens, or irrelevant antigens are depressed. These results suggest that the parasites perturb the host immune system at the level of the T cells. We have studied this possibility by examining T-cell proliferation and the production of T-cell regulatory molecules in T. cruzi-infected mice.Interleukin 2 (IL-2) appears to play a key role in the regulation of cellular immune responses (5, 6). It is produced by T lymphocytes in the presence of interleukin 1 (IL-1) and mitogen or antigen, and it sustains the proliferation of helper and effector T lymphocytes and thus amplifies the effector phase of the immune response. Because of this central role of IL-2 in regulating the immune response, we have examined its production and activity in T. cruzi-infected mice.We report here that acute infection with T. cruzi results in a severe depression of IL-2 production which parallels the depressed proliferative response to the mitogen concanavalin A (Con A). Furthermore, Thy-l-spleen cells from infected animals are able to suppress the proliferative response to Con A and, to a lesser extent, IL-2 production by spleen cells from normal animals. MATERIALS AND METHODSMice and Infection. All experiments were performed with pools of three to eight C3H/HeJ Pas male mice (Pasteur Institute, Paris). Mice were 6-8 weeks of age at the time of...

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“…However, this molecule had no "antipyretic" activity and did not produce EP either in vivo or in vitro. More interestingly, when murabutide was incubated with rabbit peritoneal cells or with human peripheral blood mononuclear cells LAF was produced although no detectable pyrogenicity could be found in the same supernatants (13). MDP itself, like most macrophage activators, is an inductor of both monokines which are sometimes referred to under the same name, i.e.…”

Section: A) Pyrogenic Activitymentioning

confidence: 99%

Muramyl Peptides as Possible Endogenous Immunopharmacological Mediators

Chedid

1983

Microbiology and Immunology

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Synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine, also called MDP for muramyl dipeptide, is a copy of a fragment of bacterial peptidoglycan. Soon after the recognition ofMDP as being the minimal subunit responsible for the activity of Freund's complete adjuvant, a great number of derivatives were synthesized. Because of their very low molecular weight it was hoped that they could retain selectively certain of the numerous effects produced by complex bacterial agents. Evidence was gathered showing MDP's direct effect on lymphocytes and on macrophages. The ensuing studies reviewed that MDP and several of its derivatives have marked immunopharmacological and neuropharmacological activities. Thus, besides being adjuvants, they are capable of producing hyperthermia by acting directly on thermoregulation centers or by inducing in vivo and in vitro endogenous pyrogens (EP). More recently, Krueger et al have shown that slow-wave sleep (SWS) factor was a muramyl peptide of a molecular weight close to 1,000 daltons. They have also shown that MDP and several of its synthetic analogs had a somnogenic activity. I t has previously been hypothesized that several of the immunological activities of the muramyl peptides could be due to biological mimicry with endogenous products. Recent observations argue in favor of the presence of an MDP bacterial structure in mammalian mediators which increase slow-wave sleep and/or produce fever. The implications of these findings will be discussed.

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Production of lymphocyte activating factor in the absence of endogenous pyrogen by rabbit or human leukocytes stimulated by a muramyl dipeptide derivative

Cited by 76 publications

References 20 publications

Leukemia cell lines can replace monocytes for mitogen-induced T-lymphocyte responses: this accessory function is dependent upon their differentiation stage.

Leukemia cell lines can replace monocytes for mitogen-induced T-lymphocyte responses: this accessory function is dependent upon their differentiation stage.

Modification of T-cell proliferation and interleukin 2 production in mice infected with Trypanosoma cruzi.

Muramyl Peptides as Possible Endogenous Immunopharmacological Mediators

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