Impaired phagocytosis of apoptotic cells causes accumulation of bone marrow-derived macrophages in aged mice
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Accumulation of tissue macrophages is a significant characteristic of disease-associated chronic inflammation, and facilitates the progression of disease pathology. However, the functional roles of these bone marrow-derived macrophages (BMDMs) in aging are unclear. Here, we identified agedependent macrophage accumulation in the bone marrow, showing that aging significantly increases the number of M1 macrophages and impairs polarization of BMDMs. We found that age-related dysregulation of BMDMs is associated with abnormal overexpression of the anti-inflammatory interleukin-10. BMDM dysregulation in aging impairs the expression levels of pro-inflammatory cytokines and genes involved in B-cell maturation and activation. Phagocytosis of apoptotic Jurkat cells by BMDMs was reduced because of low expression of phagocytic receptor CD14, indicating that increased apoptotic cells may result from defective phagocytosis of apoptotic cells in the BM of aged mice. Therefore, CD14 may represent a promising target for preventing BMDM dysregulation, and macrophage accumulation may provide diagnostic and therapeutic clues.
Abstract
Accumulation of tissue macrophages is a significant characteristic of disease-associated chronic inflammation, and facilitates the progression of disease pathology. However, the functional roles of these bone marrow-derived macrophages (BMDMs) in aging are unclear. Here, we identified agedependent macrophage accumulation in the bone marrow, showing that aging significantly increases the number of M1 macrophages and impairs polarization of BMDMs. We found that age-related dysregulation of BMDMs is associated with abnormal overexpression of the anti-inflammatory interleukin-10. BMDM dysregulation in aging impairs the expression levels of pro-inflammatory cytokines and genes involved in B-cell maturation and activation. Phagocytosis of apoptotic Jurkat cells by BMDMs was reduced because of low expression of phagocytic receptor CD14, indicating that increased apoptotic cells may result from defective phagocytosis of apoptotic cells in the BM of aged mice. Therefore, CD14 may represent a promising target for preventing BMDM dysregulation, and macrophage accumulation may provide diagnostic and therapeutic clues.
참고문헌 (29)
- Wynn TA, "Macrophage biology in development, homeostasis and disease", Nature, 496, pp.445~455 (2013)
- Pollard JW, "Trophic macrophages in development and disease", Nat Rev Immunol, 9, pp.259~270 (2009)
- Gordon S, "Alternative activation of macrophages", Nat Rev Immunol, 3, pp.23~35 (2003)
- Mosser DM, "Exploring the full spectrum of macrophage activation", Nat Rev Immunol, 8, pp.958~969 (2008)
- Mosser DM, "Interleukin-10 : new perspectives on an old cytokine", Immunol Rev, 226, pp.205~218 (2008)
- Jenkins SJ, "Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation", Science, 332, pp.1284~1288 (2011)
- Poon IK, "Apoptotic cell clearance: basic biology and therapeutic potential", Nat Rev Immunol, 14, pp.166~180 (2014)
- Amano SU, "Local proliferation of macrophages contributes to obesityassociated adipose tissue inflammation", Cell Metab, 19, pp.162~171 (2014)
- 김대인, "Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and Related with Poor Survival in Anaplastic Thyroid Cancer", Endocrinology and Metabolism, 31(3), pp.469~475 (2016), 대한내분비학회
- Ainhoa Mielgo, "Impact of tumour associated macrophages in pancreatic cancer", BMB Reports, 46(3), pp.131~138 (2013), 생화학분자생물학회
- Oh BC, "Magnetic resonance imaging contrast agent with paramagnetic-inositol phosphates complexes", US 12, 2010
- Renshaw M, "Cutting edge: impaired Toll-like receptor expression and function in aging", J Immunol, 169, pp.4697~4701 (2002)
- Moore KW, "Interleukin-10 and the interleukin-10 receptor", Annu Rev Immunol, 19, pp.683~765 (2001)
- Thangarajh M, "Expression of B-cell-activating factor of the TNF family (BAFF) and its receptors in multiple sclerosis", J Neuroimmunol, 152, pp.183~190 (2004)
- Zimmermann VS, "Engagement of B cell receptor regulates the invariant chain-dependent MHC class II presentation pathway", J Immunol, 162, pp.2495~2502 (1999)
- Shachar I, "Requirement for invariant chain in B cell maturation and function", Science, 274, pp.106~108 (1996)
- Lauber K, "Clearance of apoptotic cells: getting rid of the corpses", Mol Cell, 14, pp.277~287 (2004)
- Segawa K, "Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure", Science, 344, pp.1164~1168 (2014)
- Yoon KW, "Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53", Science, 349, pp.1261669~ (2015)
- Arandjelovic S, "Phagocytosis of apoptotic cells in homeostasis", Nat Immunol, 16, pp.907~917 (2015)
- Gregory CD, "CD14-dependent clearance of apoptotic cells: relevance to the immune system", Curr Opin Immunol, 12, pp.27~34 (2000)
- Linehan E, "Aging impairs peritoneal but not bone marrow-derived macrophage phagocytosis", Aging Cell, 13, pp.699~708 (2014)
- Plowden J, "Innate immunity in aging: impact on macrophage function", Aging Cell, 3, pp.161~167 (2004)
- Ghesquiere B, "Metabolism of stromal and immune cells in health and disease", Nature, 511, pp.167~176 (2014)
- Popi AF, "Interleukin-10 secreted by B-1 cells modulates the phagocytic activity of murine macrophages in vitro", Immunology, 113, pp.348~354 (2004)
- Amir O, "Changes in the monocytic subsets CD14(dim)CD16(+) and CD14(++)CD16(-) in chronic systolic heart failure patients", Mediators Inflamm, 2012, pp.616384~ (2012)
- Sakai K, "Absence of CD14 delays progression of prion diseases accompanied by increased microglial activation", J Virol, 87, pp.13433~13445 (2013)
- Kim OH, "beta-propeller phytase hydrolyzes insoluble Ca(2+)-phytate salts and completely abrogates the ability of phytate to chelate metal ions", Biochemistry, 49, pp.10216~10227 (2010)
- 이윤진, "Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation", BMB Reports, 48(3), pp.166~171 (2015), 생화학분자생물학회
