Abstract
Extramedullary hematopoiesis has been shown to contribute to the pathogenesis of a variety of diseases including cardiovascular diseases. In this process, the spleen is seeded with mobilized bone marrow cells that augment its hematopoietic ability. It is unclear whether these immigrant cells that are produced/reprogrammed in spleen are similar or different from those found in the bone marrow. To begin to understand this, we investigated the relative potency of adult splenocytes per se to repopulate bone marrow of lethally-irradiated mice and its functional consequences in atherosclerosis. The splenocytes were harvested from GFP donor mice and transplanted into myeloablated wild type recipient mice without the inclusion of any bone marrow helper cells. We found that adult splenocytes repopulated bone marrow of myeloablated mice and the transplanted cells differentiated into a full repertoire of myeloid cell lineages. The level of monocytes/macrophages in the bone marrow of recipient mice was dependent on the cell origin, i.e., the donor splenocytes gave rise to significantly more monocytes/macrophages than the donor bone marrow cells. This occurred despite a significantly lower number of hematopoietic stem cells being present in the donor splenocytes when compared with donor bone marrow cells. Atherosclerosis studies revealed that donor splenocytes displayed a similar level of atherogenic and atheroprotective activities to those of donor bone marrow cells. Cell culture studies showed that the phenotype of macrophages derived from spleen is different from those of bone marrow. Together, these results demonstrate that splenocytes can seed bone marrow of myeloablated mice and modulate atherosclerosis. In addition, our study shows the potential of splenocytes for therapeutic interventions in inflammatory disease.
Highlights
Current knowledge indicates that splenic hematopoiesis contributes to variety of inflammatory and degenerative diseases [1,2,3,4,5,6,7,8,9,10]
The phenotypes of donor splenocytes and bone marrow cells are shown in S2 Fig. After transplantation of doi:10.1371/journal.pone.0125961.g001
Donor splenocytes and bone marrow cells into recipient mice, the phenotypes of engrafted cells were determined by flow cytometry
Summary
Current knowledge indicates that splenic hematopoiesis contributes to variety of inflammatory and degenerative diseases [1,2,3,4,5,6,7,8,9,10]. Splenocyte Transplantation and Atherosclerosis models of disease including cancer [11], atherosclerosis [12,13,14] and myocardial infarction [15]. These studies suggest that hematopoietic stem cells originating from the bone marrow accumulate in high numbers within the spleen of diseased animals and they become more skewed toward myelopoiesis at the expense of erythropoiesis and lymphopoiesis [11]. Innate immunity, which is represented by macrophages, is necessary for the initiation of atherosclerosis [18]
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