Inhibitor of in-Vitro Granulopoiesis in Plasma of Patients With Renal Failure

Vincent, P. C.; Sutherland, Ruth; Carson, Tiffany L.; Morris, Marilyn E.; Chapman, GrahamV.

doi:10.1016/s0140-6736(78)91571-4

Cited by 18 publications

(4 citation statements)

References 16 publications

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“…More over, uremic serum had no inhibitory effect either on the in vitro growth of normal CFU-GM or on the pro duction of CSA by normal leukocytes. The last obser vation is in contrast with the data of Vincent et al [5], showing a potent inhibitor of the production of CSA in plasma of uremic patients. The different culture conditions and the use of marrow instead of blood CFU-GM as target cells may account at least in part for this difference.…”

Section: Discussioncontrasting

confidence: 93%

“…The neutrophil count in untreated chronic uremic patients is either normal or moderately increased [1], neutrophilia being prominent only in patients with pericarditis or other inflammations related to severe azotemia [2], The marrow is almost normal in uremic patients [1], However, the mobilization of neutrophils from the bone marrow reserve by hydrocortisone or etiocholanolone has been shown to be depressed in both dialyzed and nondialyzed uremic patients [3,4], Moreover, a potent inhibitor of in vitro granulopoie sis was found in the serum of nonleukopenic uremic patients, so that its significance in vivo remained un clear [5].…”

Section: Introductionmentioning

confidence: 99%

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Alterations of Granulopoiesis in Chronic Uremic Patients Treated with Intermittent Hemodialysis

Ponassi¹,

Morra²,

Gurreri³

et al. 1987

Acta Haematol

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Granulocyte-macrophage progenitor cells (CFU-GM), leukocyte colony-stimulating activity (CSA), granuloblast differentiation and proliferation and the effect of uremic serum on the in vitro growth of normal CFU-GM have been studied in 8 chronic uremic patients treated with intermittent hemodialysis three times a week. The studies were performed in the postabsorptive state twice in each patient, that is at the longest and shortest dialytic interval. CFU-GM growth in agar and leukocyte CSA did not differ significantly from the normal level in uremic subjects. The granulocytic and macrophagic differentiation in a liquid culture system was significantly reduced in uremic patients, notwithstanding the appearance of high numbers of undifferentiated blastic cells. The serum of uremic patients had no effect on normal CFU-GM and leukocyte CSA.

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Section: Discussioncontrasting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Alterations of Granulopoiesis in Chronic Uremic Patients Treated with Intermittent Hemodialysis

Ponassi¹,

Morra²,

Gurreri³

et al. 1987

Acta Haematol

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“…A variety of inhibitors, both physiological and pathological, of in vitro granulopoiesis have been identified, and it has been possible to distinguish those which inhibit CSA production from those which act directly on the CFU-C. Normal granulocytes inhibit CSA production by monocytes (Heit et al, 1974(Heit et al, , 1977Broxmeyer et al, 1978c;Mendelsohn et al, 1978), due to release of lactoferrin (Broxmeyer et aE, 1978~). Plasma from patients with chronic renal failure contains a low mol wt (<20 OOO daltons) non-dialysable inhibitor of CSA production (Vincent et al, 1978). Purified granulocyte extracts (chalones) (Aardal etal, 1977), a high mol wt substance present in normal serum (Baker & Galbraith, 1979) and leukaemic cell extracts or conditioned media (Broxmeyer et al, 1978a, b) all inhibit CFU-C directly.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Normal Human Granulopoiesis in Vitro by Non‐B Non‐T Lymphocytes

Morris¹,

Vincent²,

Sutherland³

et al. 1980

Br J Haematol

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Normal non-adherent mononuclear cells were shown to inhibit colony formation by normal human marrow cells cultured for 7 d in semi-solid agar. Inhibition was the same using cells from the marrow donor or from an unrelated normal subject, and was shown to be dose-dependent over the range of 4 X 10(5) to 6 X 10(3) mononuclear cells per 1 X 10(5) marrow cells plated. Inhibition was not seen in 14 d cultures, and it is postulated that colony-forming cells sensitive to lymphocyte inhibition belonged to the population known to give rise to colonies after 7 d in culture. Cell fractionation studies showed that inhibition was due to non-B non-T lymphocytes, purified B cells or T cells being neither inhibitory nor stimulatory. Inhibition was only shown with intact viable lymphocytes and it was not possible to extract inhibitory activity from the cells, or to produce inhibition by media conditioned by lymphocytes. The effect was apparently due to a direct action on colony-forming cells in the marrow and was not due to inhibition of colony stimulating activity (CSA) production, or to absorption or inactivation of CSA. These results emphasize the need to include appropriate controls when looking for possible cell-mediated inhibitors in disease states, particularly when 7 d cultures are used.

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“…It remains possible that their observations may be explained in part by a mecha nism whereby Epo or its receptor is bound or inactivated by CRF sera. We have found dialyzable granulopoietic inhibitory activity in some of our CRF patients [4], and Vincent et al [21 ] concluded that the inhibitory effect was due to insufficient production or inactivation of colonystimulating factors. In the present study, we were unable to detect granulopoietic inhibition by the Sephadex G-200 fractions, and in some cases the fractions en hanced CFU-GM growth.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Purification of Erythropoiesis Inhibitory Activity from Uremic Sera

Solangi¹,

Lutton²,

Ng³

et al. 1988

Nephron

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In vitro erythropoiesis inhibitory activity (EIA) was isolated and partially purified from sera obtained from a patient with chronic renal failure (CRF). EIA was purified from human sera by ammonium sulfate precipitation, column chromatography and PAGE electophoresis, and the corresponding biological activity was assayed in erythroid colony (CFU-E) cultures. Ammonium sulfate precipitation revealed that the EIA resided in two high molecular weight fractions which yielded a single peak on G-200 Sephadex. PAGE electrophoresis demonstrated that the EIA fraction separated into 3 bands with a molecular weight range of 12,000–50,000 daltons. Antibody to EIA was prepared in rabbits, and Ouchterlony immunodiffusion assays employing the antibody material revealed that several CRF sera generated intense double preciptin bands when tested in the assay. In contrast, normal sera consistently yielded a weak preciptin band. These results suggest the presence of reduced amounts of EIA-like material in normal humans and elevated levels in CRF sera. The significance of EIA in the anemia of CRF is discussed.

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Inhibitor of in-Vitro Granulopoiesis in Plasma of Patients With Renal Failure

Cited by 18 publications

References 16 publications

Alterations of Granulopoiesis in Chronic Uremic Patients Treated with Intermittent Hemodialysis

Alterations of Granulopoiesis in Chronic Uremic Patients Treated with Intermittent Hemodialysis

Inhibition of Normal Human Granulopoiesis in Vitro by Non‐B Non‐T Lymphocytes

Isolation and Purification of Erythropoiesis Inhibitory Activity from Uremic Sera

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