Objective: There are two monocyte populations in human blood: CD14+CD16-classical
monocytes and CD14+CD16+ inflammatory monocytes. CD14+CD16+inflammatory monocytes, account for
approximately 10% of the total monocytes, may be expanded in various types of inflammatory
conditions.The purpose of this study was to investigate whether the
expansion of the CD14+CD16+ monocyte population represents a risk factor of aseptic loosening (AL). Methods: Peripheral monocytes subsets were measured in revision patients with AL (n =
35) and in patients with stable implants (SI, n = 56). The gene profiles of TNFα, IL-1β, CD16, CD68 and TRAP5B from collected loosening periprosthetic
tissues were analyzed. Results: There were no significant differences in
the CD14+CD16+monocyte populations between the SI and AL patients. The CD14+CD16+ monocytes were marginally higher in revision patients with
osteolysis (n = 30), compared to patients without osteolysis (n = 5) though no
statistically difference was found. There
was an association between the CD14+CD16+ monocyte subpopulation and the tissue gene profiles, including IL-1β (p = 0.063), CD68 (p = 0.036), and
TRAP5B (p = 0.073). Conclusion: It
was demonstrated that the expansion of
CD14+CD16+ monocytes reflects, to some extent, the
inflammatory status of the loosening periprosthetic tissues. It is unclear if some
of those SI patients (no pain and negative radiograph) who have a higher
frequency of CD14+CD16+ monocytes may be at the early
stage of AL. Further evaluation of CD14+CD16+ monocyte
population, independently or combined with other factors, will be useful to
design a risk profile for AL incidence and progression.
References
[1]
Berry, D.J., Harmsen, W.S., Cabanela, M.E. and Morrey, B.F. (2002) Twenty-Five-Year Survivorship of Two Thousand Consecutive Primary Charnley Total Hip Replacements: Factors Affecting Survivorship of Acetabular and Femoral Components. The Journal of Bone and Joint Surgery, 84, 171-177. https://doi.org/10.2106/00004623-200202000-00002
[2]
Garellick, G., Malchau, H. and Herberts, P. (2000) Survival of Hip Replacements. A Comparison of a Randomized Trial and a Registry. Clinical Orthopaedics and Related Research, 375, 157-167. https://doi.org/10.1097/00003086-200006000-00019
[3]
Kurtz, S., Ong, K., Lau, E., Mowat, F. and Halpern, M. (2007) Projections of Primary and Revision Hip and Knee Arthroplasty in the United States from 2005 to 2030. The Journal of Bone and Joint Surgery, 89, 780-785.
[4]
McNamara, I.R. (2010) Impaction Bone Grafting in Revision Hip Surgery: Past, Present and Future. Cell Tissue Bank, 11, 57-73. https://doi.org/10.1007/s10561-009-9147-y
[5]
Sundfeldt, M., Carlsson, L.V., Johansson, C.B., Thomsen, P. and Gretzer, C. (2006) Aseptic Loosening, Not Only a Question of Wear: A Review of Different Theories. Acta Orthopaedica, 77, 177-197. https://doi.org/10.1080/17453670610045902
[6]
Rao, A.J., Gibon, E., Ma, T., Yao, Z., Smith, R.L. and Goodman, S.B. (2012) Revision Joint Replacement, Wear Particles, and Macrophage Polarization. Acta Biomaterialia, 8, 2815-2823.
[7]
Lin, T.H., Tamaki, Y., Pajarinen, J., Waters, H.A., Woo, D.K., Yao, Z. and Goodman, S.B. (2014) Chronic Inflammation in Biomaterial-Induced Periprosthetic Osteolysis: NF-kappaB as a Therapeutic Target. Acta Biomaterialia, 10, 1-10.
[8]
Keener, J.D., Callaghan, J.J., Goetz, D.D., Pederson, D.R., Sullivan, P.M. and Johnston, R.C. (2003) Twenty-Five-Year Results after Charnley Total Hip Arthroplasty in Patients Less than Fifty Years Old: A Concise Follow-Up of a Previous Report. The Journal of Bone and Joint Surgery, 85, 1066-1072. https://doi.org/10.2106/00004623-200306000-00013
[9]
He, T., Wu, W., Huang, Y., Zhang, X. and Tang, T. (2013) Multiple Biomarkers Analysis for the Early Detection of Prosthetic Aseptic Loosening of Hip Arthroplasty. International Orthopaedics, 37, 1025-1031. https://doi.org/10.1007/s00264-013-1837-1
[10]
Nich, C., Takakubo, Y., Pajarinen, J., Ainola, M., Salem, A., Sillat, T., Rao, A.J., Raska, M., Tamaki, Y., Takagi, M., Konttinen, Y.T., Goodman, S.B. and Gallo, J. (2013) Macrophages-Key Cells in the Response to Wear Debris from Joint Replacements. Journal of Biomedical Materials Research Part A, 101, 3033-3045. https://doi.org/10.1002/jbm.a.34599
[11]
Mertens, M.T. and Singh, J.A. (2011) Biomarkers in Arthroplasty: A Systematic Review. The Open Orthopaedics Journal, 5, 92-105. https://doi.org/10.2174/1874325001105010092
[12]
Nibbering, P.H., Leijh, P.C. and van, F.R. (1987) Quantitative Immunocytochemical Characterization of Mononuclear Phagocytes. II. Monocytes and Tissue Macrophages. Immunology, 62, 171-176.
[13]
Geissmann, F., Jung, S. and Littman, D.R. (2003) Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory Properties. Immunity, 19, 71-82.
[14]
Fujikawa, Y., Quinn, J.M., Sabokbar, A., McGee, J.O. and Athanasou, N.A. (1996) The Human Osteoclast Precursor Circulates in the Monocyte Fraction. Endocrinology, 137, 4058-4060. https://doi.org/10.1210/endo.137.9.8756585
[15]
Passlick, B., Flieger, D. and Ziegler-Heitbrock, H.W. (1989) Identification and Characterization of a Novel Monocyte Subpopulation in Human Peripheral Blood. Blood, 74, 2527-2534.
[16]
Ziegler-Heitbrock, H.W., Fingerle, G., Strobel, M., Schraut, W., Stelter, F., Schutt, C., Passlick, B. and Pforte, A. (1993) The Novel Subset of CD14+/CD16+ Blood Monocytes Exhibits Features of Tissue Macrophages. European Journal of Immunology, 23, 2053-2058. https://doi.org/10.1002/eji.1830230902
[17]
Belge, K.U., Dayyani, F., Horelt, A., Siedlar, M., Frankenberger, M., Frankenberger, B., Espevik, T. and Ziegler-Heitbrock, L. (2002) The Proinflammatory CD14+ CD16+DR++ Monocytes Are a Major Source of TNF. The Journal of Immunology, 168, 3536-3542. https://doi.org/10.4049/jimmunol.168.7.3536
[18]
Frankenberger, M., Sternsdorf, T., Pechumer, H., Pforte, A. and Ziegler-Heitbrock, H.W. (1996) Differential Cytokine Expression in Human Blood Monocyte Subpopulations: A Polymerase Chain Reaction Analysis. Blood, 87, 373-377.
[19]
Randolph, G.J., Sanchez-Schmitz, G., Liebman, R.M. and Schakel, K. (2002) The CD16 (+) (FcgammaRIII (+)) Subset of Human Monocytes Preferentially Becomes Migratory Dendritic Cells in a Model Tissue Setting. The Journal of Experimental Medicine, 196, 517-527. https://doi.org/10.1084/jem.20011608
[20]
Kawanaka, N., Yamamura, M., Aita, T., Morita, Y., Okamoto, A., Kawashima, M., Iwahashi, M., Ueno, A., Ohmoto, Y. and Makino, H. (2002) CD14+, CD16+ Blood Monocytes and Joint Inflammation in Rheumatoid Arthritis. Arthritis & Rheumatology, 46, 2578-2586. https://doi.org/10.1002/art.10545
[21]
Broker, B.M., Edwards, J.C., Fanger, M.W. and Lydyard, P.M. (1990) The Prevalence and Distribution of Macrophages Bearing Fc Gamma R I, Fc Gamma R II, and Fc Gamma R III in Synovium. Scandinavian Journal of Rheumatology, 19, 123-135. https://doi.org/10.3109/03009749009102116
[22]
Feldmann, M., Brennan, F.M. and Maini, R.N. (1996) Role of Cytokines in Rheumatoid Arthritis. Annual Review of Immunology, 14, 397-440. https://doi.org/10.1146/annurev.immunol.14.1.397
[23]
Granchi, D., Ciapetti, G., Stea, S., Savarino, L., Filippini, F., Sudanese, A., Zinghi, G. and Montanaro, L. (1999) Cytokine Release in Mononuclear Cells of Patients with Co-Cr Hip Prosthesis. Biomaterials, 20, 1079-1086.
[24]
Sabokbar, A., Fujikawa, Y., Neale, S., Murray, D.W. and Athanasou, N.A. (1997) Human Arthroplasty Derived Macrophages Differentiate into Osteoclastic Bone Resorbing Cells. Annals of the Rheumatic Diseases, 56, 414-420. https://doi.org/10.1136/ard.56.7.414
[25]
Ingham, E. and Fisher, J. (2000) Biological Reactions to Wear Debris in Total Joint Replacement. Proceedings of the Institution of Mechanical Engineers, 214, 21-37. https://doi.org/10.1243/0954411001535219
[26]
Crotti, T.N., Smith, M.D., Findlay, D.M., Zreiqat, H., Ahern, M.J., Weedon, H., Hatzinikolous, G., Capone, M., Holding, C. and Haynes, D.R. (2004) Factors Regulating Osteoclast Formation in Human Tissues Adjacent to Peri-Implant Bone Loss: Expression of Receptor Activator NFkappaB, RANK Ligand and Osteoprotegerin. Biomaterials, 25, 565-573. https://doi.org/10.1016/S0142-9612(03)00556-8
[27]
Gehrke, T., Sers, C., Morawietz, L., Fernahl, G., Neidel, J., Frommelt, L. and Krenn, V. (2003) Receptor Activator of Nuclear Factor kappaB Ligand Is Expressed in Resident and Inflammatory Cells in Aseptic and Septic Prosthesis Loosening. Scandinavian Journal of Rheumatology, 32, 287-294. https://doi.org/10.1080/03009740310003929
[28]
Lee, S.H., Brennan, F.R., Jacobs, J.J., Urban, R.M., Ragasa, D.R. and Glant, T.T. (1997) Human Monocyte/Macrophage Response to Cobalt-Chromium Corrosion Products and Titanium Particles in Patients with Total Joint Replacements. Journal of Orthopaedic Research, 15, 40-49. https://doi.org/10.1002/jor.1100150107
[29]
Miyanishi, K., Trindade, M.C., Ma, T., Goodman, S.B., Schurman, D.J. and Smith, R.L. (2003) Periprosthetic osteolysis: Induction of Vascular Endothelial Growth Factor from Human Monocyte/Macrophages by Orthopaedic Biomaterial Particles. Journal of Bone and Mineral Research, 18, 1573-1583. https://doi.org/10.1359/jbmr.2003.18.9.1573
[30]
Neale, S.D. and Athanasou, N.A. (1999) Cytokine Receptor Profile of Arthroplasty Macrophages, Foreign Body Giant Cells and Mature Osteoclasts. Acta Orthopaedica Scandinavica, 70, 452-458. https://doi.org/10.3109/17453679909000980
[31]
Ren, W.P., Wu, B., Mayton, L. and Wooley, P.H. (2002) Polyethylene and Methyl Methacrylate Particle-Stimulated Inflammatory Tissue and Macrophages Up-Regulate Bone Resorption in a Murine Neonatal Bone Resorption in a Murine Neonatal Calvaria in Vitro Organ System. Journal of Orthopaedic Research, 20, 1031-1037.
[32]
Pandey, R., Quinn, J., Joyner, C., Murray, D.W., Triffitt, J.T. and Athanasou, N.A. (1996) Arthroplasty Implant Biomaterial Particle Associated Macrophages Differentiate into Lacunar Bone Resorbing Cells. Annals of the Rheumatic Diseases, 55, 388-395. https://doi.org/10.1136/ard.55.6.388
[33]
Yano, R., Yamamura, M., Sunahori, K., Takasugi, K., Yamana, J., Kawashima, M. and Makino, H. (2007) Recruitment of CD16+ Monocytes into Synovial Tissues Is Mediated by Fractalkine and CX3CR1 in Rheumatoid Arthritis Patients. Acta Medica Okayama, 61, 89-98.
[34]
Kawanaka, N., Nagake, Y., Yamamura, M. and Makino, H. (2002) Expression of Fc Gamma Receptor III (CD16) on Monocytes during Hemodialysis in Patients with Chronic Renal Failure. Nephron, 90, 64-71. https://doi.org/10.1159/000046316
[35]
Hanai, H., Iida, T., Takeuchi, K., Watanabe, F., Yamada, M., Kikuyama, M., Maruyama, Y., Iwaoka, Y., Hirayama, K., Nagata, S. and Takai, K. (2008) Adsorptive Depletion of Elevated Proinflammatory CD14+CD16+DR++ Monocytes in Patients with Inflammatory Bowel Disease. The American Journal of Gastroenterology, 103, 1210-1216. https://doi.org/10.1111/j.1572-0241.2007.01714.x
[36]
Okamoto, H., Mizuno, K. and Horio, T. (2003) Circulating CD14+ CD16+ Monocytes Are Expanded in Sarcoidosis Patients. The Journal of Dermatology, 30, 503-509. https://doi.org/10.1111/j.1346-8138.2003.tb00424.x
[37]
Fischer-Smith, T., Croul, S., Sverstiuk, A.E., Capini, C., L’Heureux, D., Regulier, E.G., Richardson, M.W., Amini, S., Morgello, S., Khalili, K. and Rappaport, J. (2001) CNS Invasion by CD14+/CD16+ Peripheral Blood-Derived Monocytes in HIV Dementia: Perivascular Accumulation and Reservoir of HIV Infection. Journal of NeuroVirology, 7, 528-541. https://doi.org/10.1080/135502801753248114
[38]
Ren, W.P., Li, X.Y., Chen, B.D. and Wooley, P.H. (2004) Erythromycin Inhibits Wear Debris-Induced Osteoclastogenesis by Modulation of Murine Macrophage NFkB Activity. Journal of Orthopaedic Research, 22, 21-29.
[39]
Ren, W.P., Yang, S.Y., Fang, H.W., Hsu, S. and Wooley, P.H. (2003) Distinct Gene Expression of Receptor Activator of Nuclear Factor-kB and Rank Ligand in the Inflammatory Response to Variant Morphologies of UHMWPE Particles. Biomaterials, 24, 4819-4826.
[40]
Ren, W.P., Bin, W., Mayton, L. and Wooley, P.H. (2006) Erythromycin (EM) Inhibits Wear Debris-Induced Inflammatory Osteolysis in a Murine Model. Journal of Orthopaedic Research, 24, 280-290. https://doi.org/10.1002/jor.20004
[41]
Goodman, S.B., Gibon, E., Pajarinen, J., Lin, T.-H. and Keeney, M. (2014) Novel Biological Strategies for Treatment of Wear Particle-Induced Periprosthetic Osteolysis of Orthopaedic Implants for Joint Replacement. Journal of The Royal Society Interface, 11, Article ID: 20130962. https://doi.org/10.1098/rsif.2013.0962
Morawietz, L., Classen, R.A., Schroder, J.H., Dynybil, C., Perka, C., Skwara, A., Neidel, J., Gehrke, T., Frommelt, L., Hansen, T., Otto, M., Barden, B., Aigner, T., Stiehl, P., Schubert, T., Meyer-Scholten, C., Konig, A., Strobel, P., Rader, C.P., Kirschner, S., Lintner, F., Ruther, W., Bos, I., Hendrich, C., Kriegsmann, J. and Krenn, V. (2006) Proposal for a Histopathological Consensus Classification of the Periprosthetic Interface Membrane. Journal of Clinical Pathology, 59, 591-597. https://doi.org/10.1136/jcp.2005.027458
[44]
Petitprez, V., Royer, B., Desoutter, J., Guiheneuf, E., Rigolle, A., Marolleau, J.P., Kamel, S. and Guillaume, N. (2015) CD14+CD16+ Monocytes Rather than CD14+ CD51/61+ Monocytes Are a Potential Cytological Marker of Circulating Osteoclast Precursors in Multiple Myeloma. A Preliminary Study. International Journal of Laboratory Hematology, 37, 29-35. https://doi.org/10.1111/ijlh.12216
[45]
Wu, W., Zhang, X., Zhang, C., Tang, T., Ren, W. and Dai, K. (2009) Expansion of CD14 (+) CD16 (+) Peripheral Monocytes among Patients with Aseptic Loosening. Inflammation Research, 58, 561-570. https://doi.org/10.1007/s00011-009-0020-z
[46]
Ren, W., Blasier, R., Peng, X., Shi, T., Wooley, P.H. and Markel, D. (2009) Effect of Oral Erythromycin Therapy in Patients with Aseptic Loosening of Joint Prostheses. Bone, 44, 671-677.
[47]
Goodman, S.B., Knoblich, G., O’Connor, M., Song, Y., Huie, P. and Sibley, R. (1996) Heterogeneity in Cellular and Cytokine Profiles from Multiple Samples of Tissue Surrounding Revised Hip Prostheses. Journal of Biomedical Materials Research, 31, 421-428. https://doi.org/10.1002/(SICI)1097-4636(199607)31:3<421::AID-JBM17>3.0.CO;2-L
[48]
Wong, K., Yeap, W., Tai, J., Ong, S., Dang, T. and Wong, S. (2012) The Three Human Monocyte Subsets: Implications for Health and Disease. Immunologic Research, 53, 41-57. https://doi.org/10.1007/s12026-012-8297-3
[49]
Chun, L., Yoon, J., Song, Y., Huie, P., Regula, D. and Goodman, S. (1999) The Characterization of Macrophages and Osteoclasts in Tissues Harvested from Revised Total Hip Prostheses. Journal of Biomedical Materials Research, 48, 899-903. https://doi.org/10.1002/(SICI)1097-4636(1999)48:6<899::AID-JBM20>3.0.CO;2-E
[50]
Markel, D.C., Zhang, R., Shi, T., Hawkins, M. and Ren, W. (2009) Inhibitory Effects of Erythromycin on Wear Debris-Induced VEGF/Flt-1 Gene Production and Osteolysis. Inflammation Research, 58, 413-421. https://doi.org/10.1007/s00011-009-0007-9
[51]
Habermann, B., Eberhardt, C., Feld, M., Zichner, L. and Kurth, A.A. (2007) Tartrate-Resistant Acid Phosphatase 5b (TRAP 5b) as a Marker of Osteoclast Activity in the Early Phase after Cementless Total Hip Replacement. Acta Orthopaedica, 78, 221-225. https://doi.org/10.1080/17453670710013717
[52]
Landgraeber, S., Loer, F., Heep, H., Classen, T., Grabellus, F., Totsch, M. and von, K.M. (2009) Tartrate-Resistant Acid Phosphatase 5b and C-Terminal Telopeptides of Type I Collagen as Markers for Diagnosis of Aseptic Loosening after Total Hip Replacement. Archives of Orthopaedic and Trauma Surgery, 130, 441-445. https://doi.org/10.1007/s00402-009-0905-x
[53]
Heimbeck, I., Hofer, T.P., Eder, C., Wright, A.K., Frankenberger, M., Marei, A., Boghdadi, G., Scherberich, J. and Ziegler-Heitbrock, L. (2010) Standardized Single-Platform Assay for Human Monocyte Subpopulations: Lower CD14+CD16++ Monocytes in Females. Cytometry A, 77, 823-830. https://doi.org/10.1002/cyto.a.20942
[54]
Steppich, B., Dayyani, F., Gruber, R., Lorenz, R., Mack, M. and Ziegler-Heitbrock, H.W. (2000) Selective Mobilization of CD14 (+) CD16 (+) Monocytes by Exercise. Cell Physiology—American Journal of Physiology, 279, C578-C586.
[55]
Fingerle, G., Pforte, A., Passlick, B., Blumenstein, M., Strobel, M. and Ziegler-Heitbrock, H.W. (1993) The Novel Subset of CD14+/CD16+ Blood Monocytes Is Expanded in Sepsis Patients. Blood, 82, 3170-3176.
[56]
Heron, M., Grutters, J.C., van Velzen-Blad, H., Veltkamp, M., Claessen, A.M. and van den Bosch, J.M. (2008) Increased Expression of CD16, CD69, and Very Late Antigen-1 on Blood Monocytes in Active Sarcoidosis. Chest, 134, 1001-1008. https://doi.org/10.1378/chest.08-0443
[57]
Nagasawa, T., Kobayashi, H., Aramaki, M., Kiji, M., Oda, S. and Izumi, Y. (2004) Expression of CD14, CD16 and CD45RA on Monocytes from Periodontitis Patients. Journal of Periodontal Research, 39, 72-78. https://doi.org/10.1111/j.1600-0765.2004.00713.x
[58]
Nockher, W.A. and Scherberich, J.E. (1998) Expanded CD14+ CD16+ Monocyte Subpopulation in Patients with Acute and Chronic Infections Undergoing Hemodialysis. Infection and Immunity, 66, 2782-2790.
[59]
Takeyama, N., Yabuki, T., Kumagai, T., Takagi, S., Takamoto, S. and Noguchi, H. (2007) Selective Expansion of the CD14 (+)/CD16 (Bright) Subpopulation of Circulating Monocytes in Patients with Hemophagocytic Syndrome. Annals of Hematology, 86, 787-792. https://doi.org/10.1007/s00277-007-0332-4
[60]
Ben-Hur, H., Mor, G., Insler, V., Blickstein, I., mir-Zaltsman, Y., Sharp, A., Globerson, A. and Kohen, F. (1995) Menopause Is Associated with a Significant Increase in Blood Monocyte Number and a Relative Decrease in the Expression of Estrogen Receptors in Human Peripheral Monocytes. American Journal of Reproductive Immunology, 34, 363-369. https://doi.org/10.1111/j.1600-0897.1995.tb00965.x
[61]
Janols, H., Bredberg, A., Thuvesson, I., Janciauskiene, S., Grip, O. and Wullt, M. (2010) Lymphocyte and Monocyte Flow Cytometry Immunophenotyping as a Diagnostic Tool in Uncharacteristic Inflammatory Disorders. BMC Infectious Diseases, 10, 205. https://doi.org/10.1186/1471-2334-10-205