An unbalanced monocyte macrophage polarization in the bone marrow microenvironment of patients with poor graft function after allogeneic haematopoietic stem cell transplantation

Poor graft function (PGF) is a severe complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Murine studies have demonstrated that effective haematopoiesis depends on the specific bone marrow (BM) microenvironment. Increasing evidence shows that BM macrophages (M?s), which constitute an important component of BM immune microenvironment, are indispensable for the regulation of haematopoietic stem cells (HSCs) in the BM. However, little is known about the number and function of BM M?s or whether they directly interact with HSCs in PGF patients. In the current prospective case-control study, PGF patients showed a significant increase in classically activated inflammatory M?s (M1; 218 +/- 011% vs. 082 +/- 006%, P<00001), a striking reduction in alternatively activated anti-inflammatory M?s (M2; 302 +/- 031% vs. 2189 +/- 090%, P<00001), resulting in a markedly increased M1/M2 ratio (082 +/- 006 vs. 006 +/- 0002; P<00001) in the BM compared with good graft function patients. Meanwhile, standard monocyte subsets were altered in PGF patients. Dysfunctional BM M?s, which were characterized by reduced proliferation, migration and phagocytosis, were evident in PGF patients. Furthermore, BM M?s from PGF patients with high tumour necrosis factor- and interleukin 12 levels and low transforming growth factor- levels, led to impaired BM CD34(+) cell function. In summary, our data indicate that an unbalanced BM M1/M2 ratio and dysfunctional M?s may contribute to the occurrence of PGF following allo-HSCT.