Zinc Deficiency in Mice Alters Myelopoiesis and Hematopoiesis

Abstract

Suboptimal nutriture causes leukopenia, but whether this is related to a modification in hematopoiesis is unknown. A 34-d period of zinc deficiency was used to obtain moderate and severely zinc-deficient (ZD) young adult mice whose bone marrow was evaluated for alterations in hematopoiesis, myelopoiesis and lymphopoiesis by flow cytometry. Expressions of CD31 (PECAM-1) and Ly-6C were used to identify changes in marrow population composition. Identity of marrow cells was confirmed with TER119, CD45R, Ly-6G and CD11b. Cells of the erythroid lineage declined as much as 60% depending on the degree of zinc deficiency, providing new insight into the early observations of clinicians that anemia accompanied ZD in humans. The lymphoid compartment also declined 50-70% with preferential losses among pre-B cells, an underlying cause of the lymphopenia that is a part of ZD, in which loss of pre-B cells was identified by CD43,CD45R, and immunoglobulin M. Conversely, cells of the myeloid lineage increased substantially in the marrow, both in proportion and absolute numbers in all ZD mice. Granulocytic cells increased 40-60%, whereas monocytic cells nearly doubled in ZD mice. These data suggest that there are important adaptations in hematopoietic functions as zinc becomes limiting. In the immune system, the precursors of phagocytic cells, which provide innate immunity, are protected, whereas precursors of lymphocytes, which provide adaptive immunity, are down-regulated. These findings illuminate the unique response of the marrow to a nutritional stress.