title: Splenocytes seed bone marrow of myeloablated mice: implication for atherosclerosis.
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.
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Lai
authors.initials: L
authors.lastname: Wang
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Yang
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Arias
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Li
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Minghui
authors.initials: M
authors.lastname: Qin
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Ada
authors.initials: A
authors.lastname: Yukht
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Ian K
authors.initials: IK
authors.lastname: Williamson
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
authors.affiliation: Oppenheimer Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America.
authors.forename: Behrooz G
authors.initials: BG
authors.lastname: Sharifi
mesh_terms: D064591:Allografts; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D019172:Transplantation Conditioning