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CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis.

Olmes G, Büttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C - Arthritis Res. Ther. (2016)

Bottom Line: In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role.Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054, Erlangen, Germany.

ABSTRACT

Background: The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters.

Method: Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II-V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test.

Results: The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role. Cluster analysis using macrophage subtype numbers in different renal compartments revealed three main clusters showing cluster 1 dominated by class V. Clusters 2 and 3 were dominated by lupus class IV indicating that this class can be further differentiated by its macrophage population. The number of tubulointerstitial FoxP3+ cells correlated with all investigated macrophage subtypes showing the strongest association to numbers of M2a-like macrophages. Kidney function, as assessed by serum creatinine and serum urea, correlated positively with the number of total CD68+, M2a-like and M2c-like macrophages in the tubulointerstitium. In addition, total CD68+ and M2c-like macrophage numbers highly correlated with Austin activity score. Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.

Conclusion: M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

No MeSH data available.


Related in: MedlinePlus

Distribution of macrophage subsets in different International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes. Total CD68+, M1-like inducible nitric oxide synthase (iNOS)+/CD68+ double-positive, M2a-like CD206+/CD68+ double-positive and M2c-like double-positive CD163+/CD68+ macrophages were analyzed in renal biopsies from patient with lupus nephritis ISN/RPS classes II–V using immunohistochemical analysis. a Total glomerular CD68+ macrophages. b Total tubulointerstitial CD68+ macrophages. c Glomerular M1-like macrophages. d Tubulointerstitial M1-like-macrophages. e Glomerular M2a-macrophages. f Tubulointerstitial M2a-like macrophages. g Glomerulular M2c-like macrophages. h Tubulointerstitial M2c-like macrophages. Significant differences between ISN/RPS classes are marked with lines and asterisks (*p < 0.05; **p < 0.01; ***p < 0.001)
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Fig1: Distribution of macrophage subsets in different International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes. Total CD68+, M1-like inducible nitric oxide synthase (iNOS)+/CD68+ double-positive, M2a-like CD206+/CD68+ double-positive and M2c-like double-positive CD163+/CD68+ macrophages were analyzed in renal biopsies from patient with lupus nephritis ISN/RPS classes II–V using immunohistochemical analysis. a Total glomerular CD68+ macrophages. b Total tubulointerstitial CD68+ macrophages. c Glomerular M1-like macrophages. d Tubulointerstitial M1-like-macrophages. e Glomerular M2a-macrophages. f Tubulointerstitial M2a-like macrophages. g Glomerulular M2c-like macrophages. h Tubulointerstitial M2c-like macrophages. Significant differences between ISN/RPS classes are marked with lines and asterisks (*p < 0.05; **p < 0.01; ***p < 0.001)

Mentions: First, we analyzed total CD68+ macrophage infiltration in all four investigated SLE ISN/RPS classes. There was correlation between the number of infiltrating macrophages in the glomerular and tubulointerstitial compartments and SLE ISN/RPS class. The number of total CD68+ macrophages per glomerular area was greatest in class IV renal biopsies, with mean macrophage numbers about 2.5 times higher compared to SLE ISN/RPS class V (Fig. 1a; p < 0.001) and about 2.4 times higher compared to SLE ISN/RPS class II (Fig. 1a; p < 0.05). The fewest CD68+ glomerular macrophages were detected in biopsies from patients with SLE ISN/RPS class V, for which the mean was more than 2.0 times lower compared to values in patients with SLE ISN/RPS class III (Fig. 1a; p < 0.01). Differences in total macrophage infiltration in the tubulointerstitial compartment were less pronounced, with approximately two-fold maximal differences in mean values (Fig. 1b). However, there were significant differences when making the same comparisons of SLE ISN/RPS classes in relation to glomerular CD68 infiltration (Fig. 1b).Fig. 1


CD163+ M2c-like macrophages predominate in renal biopsies from patients with lupus nephritis.

Olmes G, Büttner-Herold M, Ferrazzi F, Distel L, Amann K, Daniel C - Arthritis Res. Ther. (2016)

Distribution of macrophage subsets in different International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes. Total CD68+, M1-like inducible nitric oxide synthase (iNOS)+/CD68+ double-positive, M2a-like CD206+/CD68+ double-positive and M2c-like double-positive CD163+/CD68+ macrophages were analyzed in renal biopsies from patient with lupus nephritis ISN/RPS classes II–V using immunohistochemical analysis. a Total glomerular CD68+ macrophages. b Total tubulointerstitial CD68+ macrophages. c Glomerular M1-like macrophages. d Tubulointerstitial M1-like-macrophages. e Glomerular M2a-macrophages. f Tubulointerstitial M2a-like macrophages. g Glomerulular M2c-like macrophages. h Tubulointerstitial M2c-like macrophages. Significant differences between ISN/RPS classes are marked with lines and asterisks (*p < 0.05; **p < 0.01; ***p < 0.001)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835936&req=5

Fig1: Distribution of macrophage subsets in different International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes. Total CD68+, M1-like inducible nitric oxide synthase (iNOS)+/CD68+ double-positive, M2a-like CD206+/CD68+ double-positive and M2c-like double-positive CD163+/CD68+ macrophages were analyzed in renal biopsies from patient with lupus nephritis ISN/RPS classes II–V using immunohistochemical analysis. a Total glomerular CD68+ macrophages. b Total tubulointerstitial CD68+ macrophages. c Glomerular M1-like macrophages. d Tubulointerstitial M1-like-macrophages. e Glomerular M2a-macrophages. f Tubulointerstitial M2a-like macrophages. g Glomerulular M2c-like macrophages. h Tubulointerstitial M2c-like macrophages. Significant differences between ISN/RPS classes are marked with lines and asterisks (*p < 0.05; **p < 0.01; ***p < 0.001)
Mentions: First, we analyzed total CD68+ macrophage infiltration in all four investigated SLE ISN/RPS classes. There was correlation between the number of infiltrating macrophages in the glomerular and tubulointerstitial compartments and SLE ISN/RPS class. The number of total CD68+ macrophages per glomerular area was greatest in class IV renal biopsies, with mean macrophage numbers about 2.5 times higher compared to SLE ISN/RPS class V (Fig. 1a; p < 0.001) and about 2.4 times higher compared to SLE ISN/RPS class II (Fig. 1a; p < 0.05). The fewest CD68+ glomerular macrophages were detected in biopsies from patients with SLE ISN/RPS class V, for which the mean was more than 2.0 times lower compared to values in patients with SLE ISN/RPS class III (Fig. 1a; p < 0.01). Differences in total macrophage infiltration in the tubulointerstitial compartment were less pronounced, with approximately two-fold maximal differences in mean values (Fig. 1b). However, there were significant differences when making the same comparisons of SLE ISN/RPS classes in relation to glomerular CD68 infiltration (Fig. 1b).Fig. 1

Bottom Line: In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role.Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

View Article: PubMed Central - PubMed

Affiliation: Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstr. 8-10, 91054, Erlangen, Germany.

ABSTRACT

Background: The role of macrophages in the pathogenesis of lupus nephritis, in particular their differentiation to a certain subtype (e.g., M1- or M2-like) modulating the inflammatory reaction, is unknown. Here we investigated whether the differentiation in M1- or M2-like macrophages depends on the stage of lupus nephritis and whether this correlates with clinical parameters.

Method: Using immunohistochemical analysis we analyzed renal biopsies from 68 patients with lupus nephritis (ISN/RPS classes II-V) for infiltration with M1-like (iNOS+/CD68+), M2a-like (CD206+/CD68+), M2c-like macrophages (CD163+/CD68+), and FoxP3+ regulatory T-cells. In addition, clinical parameters at the time of renal biopsy, i.e., blood pressure, proteinuria and serum urea were correlated with the macrophage infiltration using the Spearman test.

Results: The mean number of CD68+ macrophages was related to the diagnosed ISN/RPS class, showing the highest macrophage infiltration in biopsies with diffuse class IV and the lowest number in ISN/RPS class V. In all ISN/RPS classes we detected more M2c-like CD163+/CD68+ than M2a-like CD206+/CD68+ cells, while M1-macrophages played only a minor role. Cluster analysis using macrophage subtype numbers in different renal compartments revealed three main clusters showing cluster 1 dominated by class V. Clusters 2 and 3 were dominated by lupus class IV indicating that this class can be further differentiated by its macrophage population. The number of tubulointerstitial FoxP3+ cells correlated with all investigated macrophage subtypes showing the strongest association to numbers of M2a-like macrophages. Kidney function, as assessed by serum creatinine and serum urea, correlated positively with the number of total CD68+, M2a-like and M2c-like macrophages in the tubulointerstitium. In addition, total CD68+ and M2c-like macrophage numbers highly correlated with Austin activity score. Interestingly, in hypertensive lupus patients only the number of M2a-like macrophages was significantly increased compared to biopsies from normotensive lupus patients.

Conclusion: M2-like macrophages are the dominant subpopulation in human lupus nephritis and particularly, M2a subpopulations were associated with disease progression, but their role in disease progression remains unclear.

No MeSH data available.


Related in: MedlinePlus