Effects of isobaric hypoxia on murine medullary and splenic megakaryocytopoiesis.

Abstract

Hypoxia stimulates erythropoiesis and inhibits megakaryocytopoiesis in the bone marrow of mice. However, the effects of hypoxia on megakaryocytopoiesis in the spleen are unknown. Mice were exposed to hypoxia by enclosure in cages covered with dimethyl-silicone rubber membranes for 1-14 days. The mice were sacrificed at intervals after exposure to hypoxia and blood, femurs, and the spleen were analyzed. One femur and the spleen were processed for measurement of megakaryocyte diameter and number. Marrow smears were made from the other femur and stained to identify the small acetylcholinesterase-positive (SAChE+) cell, a megakaryocyte precursor. Results showed a linear increase in packed cell volumes, a decrease in platelet counts, and a cycling of splenic volume with time in hypoxia. After 14 days of hypoxia, the relative number of megakaryocytes was decreased greater than 80% in the bone marrow and spleen; SAChE + cells were decreased greater than 65%. Splenic volume and megakaryocyte concentration were altered and the absolute number of splenic megakaryocytes cycled throughout the experiment. Mean megakaryocyte diameter increased after day 10 in the marrow and was inversely related to absolute megakaryocyte number in the spleen. Changes in megakaryocyte diameter and number with hypoxia suggest a compensatory mechanism for increasing platelet production, which may be regulated separately in the bone marrow and spleen. Results of this study support the hypotheses of stem cell competition between erythropoietic and megakaryocytic cell lines, and the autoregulation of megakaryocyte size and number.