Further Evidence of the In Vivo Role of Erythropoietin or Companion Molecules Induced by Hypoxia on Proliferation and Continuing Differentiation of BFU-e in PCDC

• Published in: Blood 1981-02, Vol.57 (2), p.298-304
• Main Authors: Harigaya, Kenichi, Cronkite, Eugene P., Miller, Marilyn E., Moccia, Giuseppe
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells; Cell Differentiation; Cell Division; Cells, Cultured; Clone Cells; Environment, Controlled; Erythrocytes - cytology; Erythropoietin - metabolism; Hypoxia - metabolism; Male; Mice; Time Factors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V57.2.298.298

Normal and plethoric bone marrow cells were grown in plasma clot diffusion chambers (PCDC) implanted into the peritoneum of normal mice or mice submitted to 7 hr of hypoxia (23,000 ft) daily, on a single day or on 2 consecutive days at different times after implantation of the PCDC's. Daily discontinuous hypoxia (DDH) produced more 6-day bursts than other treatments. Hypoxia on days 1 and 2 after implantation was nearly as effective as DDH on day-6 bursts. Later bouts of hypoxia or a single hypoxic exposure on day 1 or 2 was less effective. Erythropoietin (Ep) levels were measured by bioassay on both diffusion chamber (DC) contents and serum. Serum Ep levels peaked at 160 mil/ml after a 7-hr hypoxic exposure while the DC content Ep levels were in the nondetectable range (less than 50 mU/ml). The data implies that either higher than normal Ep levels or a companion molecules(s) produced by hypoxia are required for 1–2 days early in the culture period to force an increasing number of BFU-d-e down the erythrocytic pathway and thus increase red cell production at times of need in vivo.