Enhanced recovery from thrombocytopenia and neutropenia in mice constitutively expressing a placental hematopoietic cytokine.

Abstract

Expression of the placental hormone, prolactin-like protein E (PLP-E), a potent cytokine that acts on multiple myeloid lineages, is normally restricted to pregnancy and certain hematopoietic disease states. We hypothesized that the restricted pattern of PLP-E expression is necessary to avoid hyperstimulation of myelopoiesis. To test this idea, we have produced PLP-E transgenic mice and analyzed their steady-state blood cell levels. We find that blood cell levels remain in the normal range, and thus the constitutive expression of a cytokine of pregnancy fails to overcome the tight control of hematopoietic set points for blood cell levels. In contrast, an effect of constitutive PLP-E expression is detected during the recovery from low blood platelet levels (acute thrombocytopenia) and from low granulocyte levels (acute neutropenia) but not from anemia. Mice producing high circulating concentrations of PLP-E recover more rapidly from both thrombocytopenia and neutropenia, as seen both by an earlier increase of progenitor numbers in the bone marrow and the earlier return to normal circulating blood cell levels.