Effects of hypoxia on megakaryocytopoiesis and granulopoiesis

Previous studies have reported that exposure of mice to hypoxic conditions results in a decrease in blood platelets. To further explore the effect of hypoxia on megakaryocytopoiesis, megakaryocytes and their progenitor cells (CFU-M) were studied in hypoxic mice. Mice were exposed to hypoxia by enclosure in cages covered with dimethyl-silicone rubber membranes for up to 10 d. At various times during the hypoxic and ex-hypoxic periods the total megakaryocytes and CFU-M were determined in the humerus and spleen. CFU-M were assayed in the soft gel colony forming assay using pokeweed mitogen-stimulated spleen cell conditioned medium (PWCM) as a source of colony stimulating activity. After 10 d of hypoxia, packed red cell volume (PRCV) increased to 148% of control levels and blood platelets decreased to 40% of controls. Total megakaryocytes and CFU-M per humerus decreased to 18% and 50% of controls respectively. 4 d into the ex-hypoxic phase, PRCV was still increased at 128% of controls while marrow megakaryocytes and CFU-M increased to normal levels. Platelet recovery was somewhat slower, returning to normal by d 6. In contrast to the findings in the marrow, total spleen megakaryocytes and CFU-M increased to about 3- and 5-fold of control levels respectively by 6 d of hypoxia. During the exhypoxic phase, CFU-M decreased to normal on d 4, followed by a rebound of 3-fold control values on d 8. Spleen megakaryocytes decreased more slowly, returning to normal by d 10. A marked granulocytosis was observed during the hypoxic phase.(ABSTRACT TRUNCATED AT 250 WORDS)