The Physiological Significance of an Erythropoietic Inhibitor Factor Appearing in Plasma Subsequent to Hypertransfusion*

Whitcomb, Walter H.; Moore, Margaret

doi:10.1111/j.1749-6632.1968.tb15184.x

Cited by 14 publications

(3 citation statements)

References 5 publications

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“…Inhibitors of erythropoiesis have been described in several clinical and experimental conditions. The post-hypoxic polycythemic mouse assay system has been used to demonstrate inhibitors of erythropoiesis in the plasma of high altitude dwellers brought down to sea level (Reynafarje, 1968), hyper-transfused animals (Krzymowski & Krzymowski, 1962;Whitcomb & Moore, 1968), and newborn infants (Skjaelaaren & Halvorsen, 1971;Lindemann, 1976). Recent studies have employzd the marrow suspension culture system to demonstrate immunoglobulin inhibitors of erythropoiesis in the plasma of patients with pure red cell aplasia (Krantz, 1974).…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein Inhibitor of Bqne Marrow Cells in Tumor‐bearing Rats

et al. 1979

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The role of a plasma inhibitor of erythropoiesis is evaluated in rats with Walker‐256 carcinoma (W‐256). Plasma from tumor‐bearing rats was treated by gel filtration chromatography (Sephadex G‐150) and fractions were combined into four pools on the basis of mol. wt. Inhibitory activity was assayed by adding an aliquot of the plasma fractions to normal rat marrow cells which were cultured for 24 hr with and without erythropoietin. 59Fe‐heme synthesis, [3H]thymidine DNA synthesis, and 14C‐leucine protein synthesis were studied. The results indicated that cultures containing the high mol. wt. pool (>400,000 daltons) had significantly decreased heme, DNA and protein synthesis. This inhibitor also diminished the response to erythropoietin in polycythemic mice. The lower mol. wt. pool stimulated heme synthesis in vitro. To identify the inhibitor further, plasma lipo‐protein classes were isolated by density gradient ultracentrifugation. The very low density lipoprotein (VLDL) and chylomicron fractions markedly inhibited DNA, protein and heme synthesis. Low density and high density lipoprotein fractions were inactive. A lipoprotein inhibitor of erythropoiesis was also identified in cancerous ascitic fluid, and to a lesser degree, in normal rat plasma. We suggest that this VLDL inhibitor of marrow erythropoiesis is a contributing factor in the anaemia of cancer.

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Section: Discussionmentioning

confidence: 99%

Lipoprotein Inhibitor of Bqne Marrow Cells in Tumor‐bearing Rats

et al. 1979

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“…Since Birkhill et al [10] have shown that transfusion-induced plethora suppresses red blood cell production in man, it is suggested that an erythropoiesistic inhibiting factor (EIF) exists in the plasma of hypertransfused animals [1][2][3] and in kidney homogenate [4,5,11]. We demonstrated previously that EIF exists in the plasma from pa tients with chronic renal failure [6,15] and with polycythemia vera [7], and attempted to clarify the mechanism of inhibition to ESF by uremic plasma [6,12].…”

Section: Discussionmentioning

confidence: 99%

“…

Recently, it was reported that an erythropoiesistic inhibiting factor (EIF) existed in the plasma of hypertransfuscd animals [1][2][3], and in normal rat kidney homogenate [4,5], Our previous studies also de monstrated that inhibitory activity exists in the plasma from patients with chronic renal failure [6] and with polycythemia vera [7]. These findings suggest the possibility that the normal regulation of erythro poiesis is determined by the summation effects of a stimulator, erythro poietin (ESF), and an inhibitor (EIF).

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confidence: 99%