Macrophages in normal human bone marrow and in chronic myeloproliferative disorders: An immunohistochemical and morphometric study by a new monoclonal antibody (PG-M1) on trephine biopsies

Abstract

An immunohistochemical and morphometric study was performed on routinely processed trephine biopsies of the bone marrow in 30 normal individuals and in 90 patients with various subtypes of chronic myeloproliferative disorder. Using a new monoclonal antibody (PG-M1) directed against a formalin-resistant epitope on macrophages and by employment of the Prussian blue reaction, quantitation of this cell population was feasible. Morphometric analysis revealed that the number of iron-laden macrophages represented only a fraction of the total number of histiocytic reticular cells. As could be expected, in polycythaemia rubra vera, no haemosiderin deposits were detectable, but the content of macrophages slightly exceeded that of the normal bone marrow. In chronic myeloid leukaemia 9 of 30 patients showed a significant increase in PG-M1-positive reticular cell elements. These were consistent with pseudo-Gaucher cells, sea-blue histiocytes and intermediate cell types. Primary (idiopathic) myelofibrosis-osteomyelosclerosis was characterized by a significant increase in macrophages (25 of 30 patients). Involvement of macrophages in the complex mechanisms generating bone marrow fibrosis and angiogenesis and in bone remodelling (osteosclerosis) may be responsible for this finding.

NF-κB as a Central Mediator in the Induction of TGF-β in Monocytes from Patients with Idiopathic Myelofibrosis: An Inflammatory Response Beyond the Realm of Homeostasis

“…Activation of NF-B in IMF monocytes could be utilized to induce apoptosis with exogenous TNF-␣ (46). This could be a therapeutic strategy because macrophages and M-CSF, a terminal differentiation factor for monocytes, are increased in patients with BM fibrosis (1,25,26).…”

“…Dense fibrosis prevents retrieval of adequate number of BM cells for experimental purposes. Monocytes from patients with BM fibrosis are used in this study because they: 1) could produce fibrogenic and other relevant cytokines (24), 2) are activated in vivo (18,25,26), and 3) are increased in patients with BM fibrosis (25,26).…”

Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis

“…28 One likely source is the macrophage, increased in MPD and activated in BM fibrosis. 6,17,48 Because macrophages express NK-1, 49-51 our findings might explain a potential mechanism for the activation of circulating monocytes reported for patients with myelofibrosis. 6,52 Interactions between circulating SP and NK-1 could induce cytokines.…”

“…9,14,15 Monocytes/macrophages and megakaryocytes are included in the types of cells that have roles in the pathophysiology of BM fibrosis. 6,16,17 Regardless of the underlying cause, patients with BM fibrosis have excessive proliferation of fibroblastic mesenchymal cells. 18 The fibroblasts are heterogeneous, and experimental evidence suggests that their proliferation is secondary to a clonal disorder of the hematopoietic stem cell.…”

Differential Regulation of CXCL5 by FGF2 in Osteoblastic and Endothelial Niche Cells Supports Hematopoietic Stem Cell Migration

“…In the BM of patients with clonal myeloproliferation, several characteristics, including an increase in the number of stromal cells and increases in osteosclerosis and angiogenesis, have been demonstrated [55,56]. BMSCs (bone marrow stromal cells) and MC4 OBs have an induced osteocyte-like phenotype due to long-term FGF2 treatments [57].…”