Brian A. Naughton

Phenylhydrazine-induced leukocytosis in the rat

Rats were injected with phenylhydrazine (PHZ) for periods of up to 6 months, during which time a marked leukocytosis was induced. The highest leukocyte counts occurred within 4–5 days following injection. An initial injection of 4 mg/100 gm body weight evoked a mean total leukocyte count of 129 × 103 cells/μl. Successive weekly injections of 2 mg/100 gm resulted in a mean total leukocyte count of 70 × 103 cells/μl compared to a mean total leukocyte count of 12.5 × 103 cells/μl in saline‐injected rats. Lymphocytes and monocytes accounted for approximately 75% of the total cell counts in both the PHZ‐treated and control rats. The presence of increased numbers of mononuclear cells was confirmed by Percoll gradient separation and by phase‐contrast microscopy. Although a leukocytosis was evident when using the automated Coulter electronic cell counter, it was not discernible when blood samples were counted manually in a hemocytometer by light microscopy. Histological examination of the thymus, lymph nodes, and spleen of the PHZ‐treated rats indicated that lymphocytes and monocytes were mobilized from these sites. Lymphocyte depletion was evident, and germinal centers were found in all these lymphoid organs, indicating that PHZ induced a lymphopoietic response. A possible autoimmune etiology for PHZ‐induced red blood cell destruction is discussed.

Evidence for an Erythropoietin-Stimulating Factor in Patients with Renal and Hepatic Disease

Recently, a factor was discovered in the serum of hepatectomized animals which was capable of augmenting the hepatic erythropoietin response to hypoxia when injected into normal rats. This substance was localized in the liver via an in situ perfusion technique and was termed the hepatic erythropoietic factor (HEF). Patients with kidney disease, liver disease, and combined renal and hepatic disease were studied in this report. Detectable HEF levels were found in the plasma of patients with both liver and kidney disease and were highest in anephric patients with various liver diseases. However, HEF levels were negligible in normal humans or in patients manifesting renal disease with no hepatic involvement. The data suggest that HEF-induced hepatic erythropoietin synthesis may occur in humans as well as in animals.

The effects of interferon on murine erythropoiesis.

The effects of interferon (IF) on erythropoietin (Ep) action and production were studied in mice. In comparison to control animals, Ep action in exhypoxic, polycythemic mice was significantly decreased (p less than 0.05) following two low dose injections of IF (2.9-3.5 X 10(4) units). In addition, renal Ep production in normal intact mice was also significantly decreased (p less than 0.01) following a single injection of IF (5.4-6.3 X 10(4) units) and hypoxic exposure.

Erythropoietin (Ep) Production and Kupffer Cell Alterations following Nephrectomy, Hypoxia, or Combined Nephrectomy and Hypoxia

Summary Hepatic cells were evaluated using scintillation scanning and counting, autoradiography, and planimetry under conditions favoring extrarenal Ep production. In general, Kupffer cell activity paralleled Ep production whereas the liver parenchymal cells did not manifest significant changes. The studies suggest that the Kupffer cell may be an extrarenal cellular site of Ep production.

The Effects of Prostaglandins on Extrarenal Erythropoietin Production

Abstract The E and A series prostaglandins have been reported to stimulate erythropoiesis and renal erythropoietin (Ep) production. In the present study, these prostaglandins also stimulated the elaboration of extrarenal Ep in renoprival animals after hypoxia. This extrarenal response was primarily due to hepatic Ep synthesis; when subtotal hepatectomy (hepx) was followed by nephrectomy, the Ep response to hypoxia was almost completely abolished. The synthetic methylated prostaglandins (16, 16-dimethyl E2 and (15s)-15 methyl E2) exerted the most potent effects on both the hepatic and renal Ep response. It is believed that this is attributable, at least in part, to the greater stability of these compounds in vivo. Prostaglandins do not appear to be capable of substantially elevating Ep production by the regenerating liver. When compared to vehicle- or saline-injected rats, a greater stimulation of hepatic Ep elaboration after prostaglandin treatment was observed in animals with normal livers than in rats with liver regenerating 72 hr after hepx.

The Reticuloendothelial System and Erythropoiesis

A wide diversity of functions has been ascribed to the cells of the reticuloendothelial system (RES) since that term was first coined by Aschoff and Kiyono in 1913. These cells were identified by their ability to phagocytize foreign particles and stain with vital dyes. Although these attributes were recognized by Metchnikoff as early as 1905, it was the association of these phagocytic cells with reticulum (argentophilic) fibers which first led to their definition as a reticuloendothelial system. The terms mononuclear phagocytic system and reticulohistiocytic system are synonymous with RES.