Limits...
Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy.

Silva GE, Costa RS, Ravinal RC, Ramalho LN, Reis MA, Moyses-Neto M, Romao EA, Coimbra TM, Dantas M - Clinics (Sao Paulo) (2012)

Bottom Line: Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65.We also used Southwestern histochemistry for the in situ detection of activated NF-kB.Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry).

View Article: PubMed Central - PubMed

Affiliation: University of São Paulo, Faculty of Medicine of Ribeirão Preto, Department of Pathology, Ribeirão Preto/SP, Brazil. gyleanes@fmrp.usp.br

ABSTRACT

Objectives: The objectives of our study were as follows: 1) to analyze the prognostic value of macrophage infiltration in primary IgA nephropathy (IgAN) and 2) to study the relationship between macrophages and other factors associated with the development of renal fibrosis, including mast cells, TGF-β1, α-SMA and NF-kB.

Methods: We analyzed 62 patients who had been diagnosed with IgAN between 1987 and 2003. Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65. We also used Southwestern histochemistry for the in situ detection of activated NF-kB.

Results: The infiltration of macrophages into the tubulointerstitial compartment correlated with unfavorable clinical and histological parameters, and a worse clinical course of IgAN was significantly associated with the number of tubulointerstitial macrophages. Kaplan-Meier curves demonstrated that increased macrophage infiltration was associated with decreased renal survival. Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry). In the multivariate analysis, the two parameters that correlated with macrophage infiltration, proteinuria and tubulointerstitial injury, were independently associated with an unfavorable clinical course.

Conclusion: An increased number of macrophages in the tubulointerstitial area may serve as a predictive factor for poor prognosis in patients with IgAN, and these cells were also associated with the expression of pro-fibrotic factors.

Show MeSH

Related in: MedlinePlus

Southwestern histochemistry for NF-kB expression. (A) The absence of staining and (B) moderate-to-intense staining in the tubular compartment (A and B: objective 40x).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3400157&req=5

f3-cln_67p697: Southwestern histochemistry for NF-kB expression. (A) The absence of staining and (B) moderate-to-intense staining in the tubular compartment (A and B: objective 40x).

Mentions: The presence of tubulointerstitial macrophages was not correlated with the glomerular (p = 0.50) or tubulointerstitial (p = 0.70) expression of TGF-β1 or the glomerular expression of α-SMA (p = 0.52). Macrophage numbers had a tendency to correlate with NF-kB expression, as measured by SWH (p = 0.07) and shown in Figure 3. Interestingly, the numbers of tubulointerstitial macrophages showed positive correlations with tubulointerstitial α-SMA (p = 0.01) and NF-kB expression, as measured by IHC (p<0.01), as well as tubulointerstitial injury (p<0.01) and poor clinical outcome (p = 0.01). The correlation between the presence of mast cells and macrophages infiltrating the tubulointerstitium of the kidney was also statically significant (p<0.01).


Renal macrophage infiltration is associated with a poor outcome in IgA nephropathy.

Silva GE, Costa RS, Ravinal RC, Ramalho LN, Reis MA, Moyses-Neto M, Romao EA, Coimbra TM, Dantas M - Clinics (Sao Paulo) (2012)

Southwestern histochemistry for NF-kB expression. (A) The absence of staining and (B) moderate-to-intense staining in the tubular compartment (A and B: objective 40x).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3400157&req=5

f3-cln_67p697: Southwestern histochemistry for NF-kB expression. (A) The absence of staining and (B) moderate-to-intense staining in the tubular compartment (A and B: objective 40x).
Mentions: The presence of tubulointerstitial macrophages was not correlated with the glomerular (p = 0.50) or tubulointerstitial (p = 0.70) expression of TGF-β1 or the glomerular expression of α-SMA (p = 0.52). Macrophage numbers had a tendency to correlate with NF-kB expression, as measured by SWH (p = 0.07) and shown in Figure 3. Interestingly, the numbers of tubulointerstitial macrophages showed positive correlations with tubulointerstitial α-SMA (p = 0.01) and NF-kB expression, as measured by IHC (p<0.01), as well as tubulointerstitial injury (p<0.01) and poor clinical outcome (p = 0.01). The correlation between the presence of mast cells and macrophages infiltrating the tubulointerstitium of the kidney was also statically significant (p<0.01).

Bottom Line: Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65.We also used Southwestern histochemistry for the in situ detection of activated NF-kB.Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry).

View Article: PubMed Central - PubMed

Affiliation: University of São Paulo, Faculty of Medicine of Ribeirão Preto, Department of Pathology, Ribeirão Preto/SP, Brazil. gyleanes@fmrp.usp.br

ABSTRACT

Objectives: The objectives of our study were as follows: 1) to analyze the prognostic value of macrophage infiltration in primary IgA nephropathy (IgAN) and 2) to study the relationship between macrophages and other factors associated with the development of renal fibrosis, including mast cells, TGF-β1, α-SMA and NF-kB.

Methods: We analyzed 62 patients who had been diagnosed with IgAN between 1987 and 2003. Immunohistochemical staining was performed with monoclonal antibodies against CD68 and mast cell tryptase and polyclonal antibodies against TGF-β1, α-SMA and NF-kB p65. We also used Southwestern histochemistry for the in situ detection of activated NF-kB.

Results: The infiltration of macrophages into the tubulointerstitial compartment correlated with unfavorable clinical and histological parameters, and a worse clinical course of IgAN was significantly associated with the number of tubulointerstitial macrophages. Kaplan-Meier curves demonstrated that increased macrophage infiltration was associated with decreased renal survival. Moreover, the presence of macrophages was associated with mast cells, tubulointerstitial α-SMA expression and NF-kB activation (IH and Southwestern histochemistry). In the multivariate analysis, the two parameters that correlated with macrophage infiltration, proteinuria and tubulointerstitial injury, were independently associated with an unfavorable clinical course.

Conclusion: An increased number of macrophages in the tubulointerstitial area may serve as a predictive factor for poor prognosis in patients with IgAN, and these cells were also associated with the expression of pro-fibrotic factors.

Show MeSH
Related in: MedlinePlus