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Clinical significance of monocyte heterogeneity.

Stansfield BK, Ingram DA - Clin Transl Med (2015)

Bottom Line: Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages.Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen.In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics and Neonatal-Perinatal Medicine, Georgia Regents University, Augusta, Georgia ; Vascular Biology Center, Georgia Regents University, Augusta, Georgia ; Medical College of Georgia at Georgia Regents University, 1120 15th St, BIW-6033, Augusta, GA 30912 USA.

ABSTRACT
Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis.

No MeSH data available.


Related in: MedlinePlus

Sample gating strategy showing three human monocyte populations based on expression of CD14 and CD16. Relative expression of CD14 (x-axis) and CD16 (y-axis) is demonstrated on log scale. Classical monocytes (CD14++CD16−) are gated in the green box, intermediate monocytes (CD14++CD16+) in the red box, and non-classical monocytes (CD14+CD16++) in the lavender box.
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Fig1: Sample gating strategy showing three human monocyte populations based on expression of CD14 and CD16. Relative expression of CD14 (x-axis) and CD16 (y-axis) is demonstrated on log scale. Classical monocytes (CD14++CD16−) are gated in the green box, intermediate monocytes (CD14++CD16+) in the red box, and non-classical monocytes (CD14+CD16++) in the lavender box.

Mentions: Until the late 1980s, monocytes were considered to represent a single population of circulating hematopoietic cells derived from the common myeloid progenitor cell in the bone marrow. The seminal work of Passlik et al. demonstrated that distinct monocyte subsets could be identified based on the expression of the surface antigen CD16 [1]. “Classical” monocytes do not express the CD16 antigen (CD14++CD16−), while “non-classical” monocytes are smaller in size and express CD16 on the cell surface (CD14+CD16++) [1]. The expression pattern of the two surface markers lends some insight into their function. CD14 acts as a co-receptor for toll-like receptor 4 and mediates lipopolysaccharide (LPS) signaling, while the CD16 antigen is identified as FcγRIIIa and participates in innate immunity [2,3]. The subsequent two decades have yielded considerable insight into the role of each cell population in human disease; however, the recent emergence of an intermediate monocyte population denoted as CD14++CD16+ has shifted focus away from this simple classification system [4-8] (Figure 1). As of 2010, three distinct monocyte populations outlined by Ziegler-Heitbrock et al. are officially recognized: CD14++CD16− (classical), CD14++CD16+ (intermediate), and CD14+CD16++ (non-classical) [4]. We will adhere to the official nomenclature for this review article.Figure 1


Clinical significance of monocyte heterogeneity.

Stansfield BK, Ingram DA - Clin Transl Med (2015)

Sample gating strategy showing three human monocyte populations based on expression of CD14 and CD16. Relative expression of CD14 (x-axis) and CD16 (y-axis) is demonstrated on log scale. Classical monocytes (CD14++CD16−) are gated in the green box, intermediate monocytes (CD14++CD16+) in the red box, and non-classical monocytes (CD14+CD16++) in the lavender box.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384980&req=5

Fig1: Sample gating strategy showing three human monocyte populations based on expression of CD14 and CD16. Relative expression of CD14 (x-axis) and CD16 (y-axis) is demonstrated on log scale. Classical monocytes (CD14++CD16−) are gated in the green box, intermediate monocytes (CD14++CD16+) in the red box, and non-classical monocytes (CD14+CD16++) in the lavender box.
Mentions: Until the late 1980s, monocytes were considered to represent a single population of circulating hematopoietic cells derived from the common myeloid progenitor cell in the bone marrow. The seminal work of Passlik et al. demonstrated that distinct monocyte subsets could be identified based on the expression of the surface antigen CD16 [1]. “Classical” monocytes do not express the CD16 antigen (CD14++CD16−), while “non-classical” monocytes are smaller in size and express CD16 on the cell surface (CD14+CD16++) [1]. The expression pattern of the two surface markers lends some insight into their function. CD14 acts as a co-receptor for toll-like receptor 4 and mediates lipopolysaccharide (LPS) signaling, while the CD16 antigen is identified as FcγRIIIa and participates in innate immunity [2,3]. The subsequent two decades have yielded considerable insight into the role of each cell population in human disease; however, the recent emergence of an intermediate monocyte population denoted as CD14++CD16+ has shifted focus away from this simple classification system [4-8] (Figure 1). As of 2010, three distinct monocyte populations outlined by Ziegler-Heitbrock et al. are officially recognized: CD14++CD16− (classical), CD14++CD16+ (intermediate), and CD14+CD16++ (non-classical) [4]. We will adhere to the official nomenclature for this review article.Figure 1

Bottom Line: Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages.Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen.In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics and Neonatal-Perinatal Medicine, Georgia Regents University, Augusta, Georgia ; Vascular Biology Center, Georgia Regents University, Augusta, Georgia ; Medical College of Georgia at Georgia Regents University, 1120 15th St, BIW-6033, Augusta, GA 30912 USA.

ABSTRACT
Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis.

No MeSH data available.


Related in: MedlinePlus