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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

Association between hypertension and macrophage subtypes. Numbers of total CD68-positive, M2a-like and M2c-like macrophages were analyzed in normotensive and hypertensive patients with lupus nephritis. a Comparison of glomerular total CD68-positive macrophage infiltration. b Comparison of tubulointerstitial total CD68-positive macrophage infiltration. c Comparison of glomerular M2a-like macrophage infiltration. d Comparison of tubulointerstitial M2a-like macrophage infiltration. e Comparison of glomerular M2c-like macrophage infiltration. f Comparison of tubulointerstitial M2c-like macrophage infiltration. Significant differences, as assessed by the Mann-Whitney U rank test, are marked by asterisks (*p < 0.013)
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Fig6: Association between hypertension and macrophage subtypes. Numbers of total CD68-positive, M2a-like and M2c-like macrophages were analyzed in normotensive and hypertensive patients with lupus nephritis. a Comparison of glomerular total CD68-positive macrophage infiltration. b Comparison of tubulointerstitial total CD68-positive macrophage infiltration. c Comparison of glomerular M2a-like macrophage infiltration. d Comparison of tubulointerstitial M2a-like macrophage infiltration. e Comparison of glomerular M2c-like macrophage infiltration. f Comparison of tubulointerstitial M2c-like macrophage infiltration. Significant differences, as assessed by the Mann-Whitney U rank test, are marked by asterisks (*p < 0.013)

Mentions: After testing for normal distribution of values using Kolmogorov-Smirnov test and finding that many datasets are not normally distributed, data were analyzed using the Kruskal-Wallis test and Dunn’s multiple comparison test post hoc test for comparison of SLE ISN/RPS classes. In all tests p < 0.05 was accepted as statistically significant. Most data are presented as scatter dot plots and only the ratios of M1-like to M2-like macrophages and Fig. 6 are presented as bars, all indicating the mean ± SEM. Spearman’s test was used to test correlation between renal macrophage infiltration and renal injury scores or clinical data. Association between macrophage infiltration and hypertension was tested using the Mann-Whitney rank test. Statistical analyses were performed using SPSS for Windows software (version 19.0 SPSS, IBM, Munich, Germany) or GraphPad Prism 5 for Windows software (version 5.02, GraphPad software Inc., San Diego, CA, USA).


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)

Association between hypertension and macrophage subtypes. Numbers of total CD68-positive, M2a-like and M2c-like macrophages were analyzed in normotensive and hypertensive patients with lupus nephritis. a Comparison of glomerular total CD68-positive macrophage infiltration. b Comparison of tubulointerstitial total CD68-positive macrophage infiltration. c Comparison of glomerular M2a-like macrophage infiltration. d Comparison of tubulointerstitial M2a-like macrophage infiltration. e Comparison of glomerular M2c-like macrophage infiltration. f Comparison of tubulointerstitial M2c-like macrophage infiltration. Significant differences, as assessed by the Mann-Whitney U rank test, are marked by asterisks (*p < 0.013)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835936&req=5

Fig6: Association between hypertension and macrophage subtypes. Numbers of total CD68-positive, M2a-like and M2c-like macrophages were analyzed in normotensive and hypertensive patients with lupus nephritis. a Comparison of glomerular total CD68-positive macrophage infiltration. b Comparison of tubulointerstitial total CD68-positive macrophage infiltration. c Comparison of glomerular M2a-like macrophage infiltration. d Comparison of tubulointerstitial M2a-like macrophage infiltration. e Comparison of glomerular M2c-like macrophage infiltration. f Comparison of tubulointerstitial M2c-like macrophage infiltration. Significant differences, as assessed by the Mann-Whitney U rank test, are marked by asterisks (*p < 0.013)
Mentions: After testing for normal distribution of values using Kolmogorov-Smirnov test and finding that many datasets are not normally distributed, data were analyzed using the Kruskal-Wallis test and Dunn’s multiple comparison test post hoc test for comparison of SLE ISN/RPS classes. In all tests p < 0.05 was accepted as statistically significant. Most data are presented as scatter dot plots and only the ratios of M1-like to M2-like macrophages and Fig. 6 are presented as bars, all indicating the mean ± SEM. Spearman’s test was used to test correlation between renal macrophage infiltration and renal injury scores or clinical data. Association between macrophage infiltration and hypertension was tested using the Mann-Whitney rank test. Statistical analyses were performed using SPSS for Windows software (version 19.0 SPSS, IBM, Munich, Germany) or GraphPad Prism 5 for Windows software (version 5.02, GraphPad software Inc., San Diego, CA, USA).

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