Heterogeneity of Monocytes and Monocyte-derived Cells in Human Lymph Nodes and Bone Marrow

Download or read book Heterogeneity of Monocytes and Monocyte-derived Cells in Human Lymph Nodes and Bone Marrow written by Marwan Qubaja and published by . This book was released on 2008 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt: Background: Human monocytes originate in the bone marrow from a common myeloid progenitor, and they are then released into the peripheral blood. Circulating monocytes are capable of differentiating into morphologically and functionally heterogeneous effector cells, including macrophages and dendritic cells. Based on CD14 and CD16 expression, human peripheral blood monocytes can be divided into a major CD14highCD16- population and two minor CD14highCD16+ and CD14dimCD16+ subpopulations. Objective: We aimed to study the heterogeneity of monocytes and monocyte-derived cells in human bone marrow and lymph nodes, in reactive and tumoral states, with the help of new monocyte/macrophage-derived markers evaluable on paraffin-embedded tissue. Materials and Methods: For this purpose, we studied a series of 33 bone marrow biopsies (BMBs) consisted of 8 normal BMBs, 15 cases of chronic myelomonocytic leukemia (CMML) and 10 cases of chronic myeloid leukemia (CML). We also studied a series of 27 lymph node biopsies including 15 biopsies of reactive lymph nodes and 12 diffuse large B cell lymphoma (DLBCL) nodal biopsies. We evaluated the expression of the following markers on bone marrow and lymph node biopsies: MPO, CD68 (KP1 and PG-M1), CD15, Glycophorin C, CD14, CD16, CD169, CD163, DC-SIGN, CD1a, CD11c, and CD123. Results: In normal BMBs, we clearly identified CD14+ monocytes with mono or bilobated nuclei, very difficult to differentiate from some neutrophils on morphology. These CD14+ monocytes were negative for PG-M1 and CD163. CD16+ monocytes were extremely rare on normal BMBs. Medullary macrophages and granulocytes were CD14-. We showed a significant expansion of dispersed CD14+ monocytes in CMML compared to CML and normal BMBs, but no increase in CD16+ monocytes. We also showed a significant decrease in the number of granulocytes expressing MPO, CD15 and CD16 in CMML, probably related to dysgranulopoiesis often encounterd in this disease. In reactive human lymph nodes, we showed that most sinusoidal histiocytes were strongly positive for CD14, CD16, CD169, and DC-SIGN. CD163 and CD11c variably stained sinusoidal histiocytes and a few cells in the germinal center having the morphology of dendritic cells. However, sinusoidal histiocytes with erythrophagocytosis lacked CD14, but expressed CD16 and CD169. In the lymph nodes of Kikuchi Fujimoto's disease, we demonstrated a strong expansion of the number of MPO+ monocyte-derived cells, and numerous monocyte-derived cells were also positive for CD123, CD14, CD11c and CD163. In DLBCL, we demonstrated a strong expansion of CD14+ monocyte-derived cells, except in cases associated with numerous mitosis, apoptotic bodies, and tingible body macrophages. We showed no increase in number of monocyte-derived cells positive for CD169, CD1a or DC-SIGN. Conclusion: We demonstrated that CD14 immunostaining makes it possible to clearly identify the rare monocyte population on normal BMBs and this is therefore useful for the histopathological diagnosis of CMML, being probably mainly associated with the expansion of the CD14+CD16- monocyte subpopulation. We also demonstrated the morphological and phenotypical heterogeneity of monocyte-derived cells in human lymph nodes. In reactive human lymph nodes, sinusoidal histiocytes are CD14+CD16+ whereas these sinusoidal histiocytes with erythrophagocytosis are CD14-CD16+. DLBCL is associated with the presence of numerous CD14+ monocyte-derived cells except in cases where numerous mitosis and tingible body macrophages are found. Whether these phenotypical changes are due to the recruitment of a different monocyte subpopulation (CD14+CD16-, CD14-CD16+) or to a downregulation of some receptors remains to be demonstrated. However, these changes are probably linked to the differential effector functions of these monocyte-derived cells.