We agree with Dr. Ritchlin that our in vitro demonstration that human osteoclast precursors are within the proliferative monocyte subpopulation must be interpreted with caution; we also support his comments that the importance of the proliferative subset in rheumatoid and psoriatic arthritis should be examined. As a point of clarification, the presence and surface phenotyping of this immature proliferative subset in the blood of many donors, as well as the suggestion of its possible relevance to inflammatory/autoimmune conditions, have been reported in a number of previous publications from our laboratory [1-5]. Also, those interested are referred to a recent publication where human osteoclasts could be generated, and potentially in large numbers, from a precursor population derived in turn from hemopoietic stem cells [6].
Dr Ritchlin also raises important questions as to whether the proliferative monocyte subpopulation expresses higher cell surface levels of c-Fms to account for the increased proliferative capacity and whether it expresses a unique surface marker(s). We have not been able to observe any differential expression of c-Fms and no unique surface marker has yet been found, although there is evidence that the subpopulation has altered expression of certain myeloid markers compared with other monocyte populations [5]. As Dr. Ritchlin states, the quest for such a marker(s) on osteoclast precursors should continue so that they can be better characterized.
1. Cheung DL, Hamilton JA: Regulation of human monocyte DNA synthesis by colony-stimulating factors, cytokines, and cyclic adenosine monophosphate. Blood 1992, 79(8):1972-1981. 2. Finnin M, Hamilton JA, Moss ST: Characterization of a CSF-induced proliferating subpopulation of human peripheral blood monocytes by surface marker expression and cytokine production. J Leukoc Biol 1999, 66(6):953-960. 3. Finnin M, Hamilton JA, Moss ST: Direct comparison of the effects of CSF-1 (M-CSF) and GM-CSF on human monocyte DNA synthesis and CSF receptor expression. J Interferon Cytokine Res 1999, 19(4):417-423. 4. Moss ST, Hamilton JA: Proliferation of a subpopulation of human peripheral blood monocytes in the presence of colony stimulating factors may contribute to the inflammatory process in diseases such as rheumatoid arthritis. Immunobiology 2000, 202(1):18-25. 5. Clanchy FI, Holloway AC, Lari R, Cameron PU, Hamilton JA: Detection and properties of the human proliferative monocyte subpopulation. J Leukoc Biol 2006, 79(4):757-766. 6. Way KJ, Dinh H, Keene MR, White KE, Clanchy FI, Lusby P, Roiniotis J, Cook AD, Cassady AI, Curtis DJ et al: The generation and properties of human macrophage populations from hemopoietic stem cells. J Leukoc Biol 2009, 85(5):766-778.
Response to Editorial by C Ritchlin...
22 July 2009
We agree with Dr. Ritchlin that our in vitro demonstration that human osteoclast precursors are within the proliferative monocyte subpopulation must be interpreted with caution; we also support his comments that the importance of the proliferative subset in rheumatoid and psoriatic arthritis should be examined. As a point of clarification, the presence and surface phenotyping of this immature proliferative subset in the blood of many donors, as well as the suggestion of its possible relevance to inflammatory/autoimmune conditions, have been reported in a number of previous publications from our laboratory [1-5]. Also, those interested are referred to a recent publication where human osteoclasts could be generated, and potentially in large numbers, from a precursor population derived in turn from hemopoietic stem cells [6].
Dr Ritchlin also raises important questions as to whether the proliferative monocyte subpopulation expresses higher cell surface levels of c-Fms to account for the increased proliferative capacity and whether it expresses a unique surface marker(s). We have not been able to observe any differential expression of c-Fms and no unique surface marker has yet been found, although there is evidence that the subpopulation has altered expression of certain myeloid markers compared with other monocyte populations [5]. As Dr. Ritchlin states, the quest for such a marker(s) on osteoclast precursors should continue so that they can be better characterized.
1. Cheung DL, Hamilton JA: Regulation of human monocyte DNA synthesis by colony-stimulating factors, cytokines, and cyclic adenosine monophosphate. Blood 1992, 79(8):1972-1981.
2. Finnin M, Hamilton JA, Moss ST: Characterization of a CSF-induced proliferating subpopulation of human peripheral blood monocytes by surface marker expression and cytokine production. J Leukoc Biol 1999, 66(6):953-960.
3. Finnin M, Hamilton JA, Moss ST: Direct comparison of the effects of CSF-1 (M-CSF) and GM-CSF on human monocyte DNA synthesis and CSF receptor expression. J Interferon Cytokine Res 1999, 19(4):417-423.
4. Moss ST, Hamilton JA: Proliferation of a subpopulation of human peripheral blood monocytes in the presence of colony stimulating factors may contribute to the inflammatory process in diseases such as rheumatoid arthritis. Immunobiology 2000, 202(1):18-25.
5. Clanchy FI, Holloway AC, Lari R, Cameron PU, Hamilton JA: Detection and properties of the human proliferative monocyte subpopulation. J Leukoc Biol 2006, 79(4):757-766.
6. Way KJ, Dinh H, Keene MR, White KE, Clanchy FI, Lusby P, Roiniotis J, Cook AD, Cassady AI, Curtis DJ et al: The generation and properties of human macrophage populations from hemopoietic stem cells. J Leukoc Biol 2009, 85(5):766-778.
Competing interests
None declared