Limits...
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

Immunohistochemical double-staining in different International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes for macrophage subsets. Representative double-staining for the different macrophage subsets using immunohistochemical analysis are shown. a M1-like macrophages (example from ISN/RPS IV biopsy) were double-positive (violet and violet arrowhead) for inducible nitric oxide synthase (iNOS) (red) and CD68 (blue and blue arrowheads). b M2a-like macrophages (example from ISN/RPS IV biopsy) were double-positive (violet, e.g., violet arrowheads) CD206 (red) and CD68 (blue and blue arrowheads). c M2c-like macrophages (example from ISN/RPS III) were double-positive (violet, e.g., viola arrowheads) CD163 (red) and CD68 (blue and blue arrowheads). d Regulatory T cells (example from ISN/RPS IV biopsy) were positive for forkhead-box-protein P3 (FoxP3) (purple and purple arrowheads) and M2c-like CD163+ macrophages (blue). e Negative control using normal mouse IgG (example from ISN/RPS IV biopsy). f Negative control using secondary antibody only (example from ISN/RPS IV biopsy)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Immunohistochemical double-staining in different International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes for macrophage subsets. Representative double-staining for the different macrophage subsets using immunohistochemical analysis are shown. a M1-like macrophages (example from ISN/RPS IV biopsy) were double-positive (violet and violet arrowhead) for inducible nitric oxide synthase (iNOS) (red) and CD68 (blue and blue arrowheads). b M2a-like macrophages (example from ISN/RPS IV biopsy) were double-positive (violet, e.g., violet arrowheads) CD206 (red) and CD68 (blue and blue arrowheads). c M2c-like macrophages (example from ISN/RPS III) were double-positive (violet, e.g., viola arrowheads) CD163 (red) and CD68 (blue and blue arrowheads). d Regulatory T cells (example from ISN/RPS IV biopsy) were positive for forkhead-box-protein P3 (FoxP3) (purple and purple arrowheads) and M2c-like CD163+ macrophages (blue). e Negative control using normal mouse IgG (example from ISN/RPS IV biopsy). f Negative control using secondary antibody only (example from ISN/RPS IV biopsy)

Mentions: For characterization of macrophage polarization we performed immunohistochemical double staining combining the pan-macrophage marker CD68 with iNOS to detect M1-like macrophages (Fig. 2a), with CD206 to detect M2a-like macrophages (Fig. 2b) and with CD163 to detect M2c-like macrophages (Fig. 2c).Fig. 2


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)

Immunohistochemical double-staining in different International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes for macrophage subsets. Representative double-staining for the different macrophage subsets using immunohistochemical analysis are shown. a M1-like macrophages (example from ISN/RPS IV biopsy) were double-positive (violet and violet arrowhead) for inducible nitric oxide synthase (iNOS) (red) and CD68 (blue and blue arrowheads). b M2a-like macrophages (example from ISN/RPS IV biopsy) were double-positive (violet, e.g., violet arrowheads) CD206 (red) and CD68 (blue and blue arrowheads). c M2c-like macrophages (example from ISN/RPS III) were double-positive (violet, e.g., viola arrowheads) CD163 (red) and CD68 (blue and blue arrowheads). d Regulatory T cells (example from ISN/RPS IV biopsy) were positive for forkhead-box-protein P3 (FoxP3) (purple and purple arrowheads) and M2c-like CD163+ macrophages (blue). e Negative control using normal mouse IgG (example from ISN/RPS IV biopsy). f Negative control using secondary antibody only (example from ISN/RPS IV biopsy)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Immunohistochemical double-staining in different International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes for macrophage subsets. Representative double-staining for the different macrophage subsets using immunohistochemical analysis are shown. a M1-like macrophages (example from ISN/RPS IV biopsy) were double-positive (violet and violet arrowhead) for inducible nitric oxide synthase (iNOS) (red) and CD68 (blue and blue arrowheads). b M2a-like macrophages (example from ISN/RPS IV biopsy) were double-positive (violet, e.g., violet arrowheads) CD206 (red) and CD68 (blue and blue arrowheads). c M2c-like macrophages (example from ISN/RPS III) were double-positive (violet, e.g., viola arrowheads) CD163 (red) and CD68 (blue and blue arrowheads). d Regulatory T cells (example from ISN/RPS IV biopsy) were positive for forkhead-box-protein P3 (FoxP3) (purple and purple arrowheads) and M2c-like CD163+ macrophages (blue). e Negative control using normal mouse IgG (example from ISN/RPS IV biopsy). f Negative control using secondary antibody only (example from ISN/RPS IV biopsy)
Mentions: For characterization of macrophage polarization we performed immunohistochemical double staining combining the pan-macrophage marker CD68 with iNOS to detect M1-like macrophages (Fig. 2a), with CD206 to detect M2a-like macrophages (Fig. 2b) and with CD163 to detect M2c-like macrophages (Fig. 2c).Fig. 2

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