Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy

Potential role in mesangial matrix expansion

Yohei Ikezumi, Toshiaki Suzuki, Tamaki Karasawa, Hiroya Hasegawa, Takeshi Yamada, Naofumi Imai, Ichiei Narita, Hiroshi Kawachi, Kevan R. Polkinghorne, David J. Nikolic-Paterson, Makoto Uchiyama

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Aims: New onset of the clinical symptoms of immunoglobulin A (IgA) nephropathy (IgAN) manifests with proliferative glomerular lesions in children, whereas adults exhibit mesangial matrix expansion and interstitial fibrosis. Alternatively, activated (M2) macrophages have been implicated in promoting tissue fibrosis in some settings. Therefore, the aim of this study was to investigate whether M2 macrophages are present in new-onset IgAN and if they are related to pathological differences between paediatric and adult disease. Methods and results: Biopsy specimens from paediatric (<10years, n=14; >12years, n=15) and adult (n=27) IgAN showed a significant infiltrate of CD68+ macrophages. M2 macrophages, identified by CD163 or CD204 expression, were detected in glomeruli and the interstitium, being more prominent in adults versus young children. CD163+ and CD204+ macrophages were present in areas of fibrosis containing myofibroblasts, and double staining showed that CD163+ cells produced the profibrotic molecule, connective tissue growth factor. In young children, total CD68+ macrophages, but not M2 macrophages, correlated with glomerular hypercellularity. In contrast, in adults and older children, mesangial matrix expansion correlated with M2 macrophages but not with the total CD68+ macrophage infiltrate. Conclusions: Alternatively activated M2 macrophages are present in new-onset paediatric and adult IgAN, and this population may promote the development of fibrotic lesions.

Original languageEnglish
Pages (from-to)198-210
Number of pages13
JournalHistopathology
Volume58
Issue number2
DOIs
Publication statusPublished - 01-01-2011
Externally publishedYes

Fingerprint

IGA Glomerulonephritis
Macrophages
Pediatrics
Immunoglobulin A
Fibrosis
Connective Tissue Growth Factor
Myofibroblasts
Young Adult

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology

Cite this

Ikezumi, Yohei ; Suzuki, Toshiaki ; Karasawa, Tamaki ; Hasegawa, Hiroya ; Yamada, Takeshi ; Imai, Naofumi ; Narita, Ichiei ; Kawachi, Hiroshi ; Polkinghorne, Kevan R. ; Nikolic-Paterson, David J. ; Uchiyama, Makoto. / Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy : Potential role in mesangial matrix expansion. In: Histopathology. 2011 ; Vol. 58, No. 2. pp. 198-210.
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abstract = "Aims: New onset of the clinical symptoms of immunoglobulin A (IgA) nephropathy (IgAN) manifests with proliferative glomerular lesions in children, whereas adults exhibit mesangial matrix expansion and interstitial fibrosis. Alternatively, activated (M2) macrophages have been implicated in promoting tissue fibrosis in some settings. Therefore, the aim of this study was to investigate whether M2 macrophages are present in new-onset IgAN and if they are related to pathological differences between paediatric and adult disease. Methods and results: Biopsy specimens from paediatric (<10years, n=14; >12years, n=15) and adult (n=27) IgAN showed a significant infiltrate of CD68+ macrophages. M2 macrophages, identified by CD163 or CD204 expression, were detected in glomeruli and the interstitium, being more prominent in adults versus young children. CD163+ and CD204+ macrophages were present in areas of fibrosis containing myofibroblasts, and double staining showed that CD163+ cells produced the profibrotic molecule, connective tissue growth factor. In young children, total CD68+ macrophages, but not M2 macrophages, correlated with glomerular hypercellularity. In contrast, in adults and older children, mesangial matrix expansion correlated with M2 macrophages but not with the total CD68+ macrophage infiltrate. Conclusions: Alternatively activated M2 macrophages are present in new-onset paediatric and adult IgAN, and this population may promote the development of fibrotic lesions.",
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Ikezumi, Y, Suzuki, T, Karasawa, T, Hasegawa, H, Yamada, T, Imai, N, Narita, I, Kawachi, H, Polkinghorne, KR, Nikolic-Paterson, DJ & Uchiyama, M 2011, 'Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy: Potential role in mesangial matrix expansion', Histopathology, vol. 58, no. 2, pp. 198-210. https://doi.org/10.1111/j.1365-2559.2011.03742.x

Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy : Potential role in mesangial matrix expansion. / Ikezumi, Yohei; Suzuki, Toshiaki; Karasawa, Tamaki; Hasegawa, Hiroya; Yamada, Takeshi; Imai, Naofumi; Narita, Ichiei; Kawachi, Hiroshi; Polkinghorne, Kevan R.; Nikolic-Paterson, David J.; Uchiyama, Makoto.

In: Histopathology, Vol. 58, No. 2, 01.01.2011, p. 198-210.

Research output: Contribution to journalArticle

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T1 - Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy

T2 - Potential role in mesangial matrix expansion

AU - Ikezumi, Yohei

AU - Suzuki, Toshiaki

AU - Karasawa, Tamaki

AU - Hasegawa, Hiroya

AU - Yamada, Takeshi

AU - Imai, Naofumi

AU - Narita, Ichiei

AU - Kawachi, Hiroshi

AU - Polkinghorne, Kevan R.

AU - Nikolic-Paterson, David J.

AU - Uchiyama, Makoto

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N2 - Aims: New onset of the clinical symptoms of immunoglobulin A (IgA) nephropathy (IgAN) manifests with proliferative glomerular lesions in children, whereas adults exhibit mesangial matrix expansion and interstitial fibrosis. Alternatively, activated (M2) macrophages have been implicated in promoting tissue fibrosis in some settings. Therefore, the aim of this study was to investigate whether M2 macrophages are present in new-onset IgAN and if they are related to pathological differences between paediatric and adult disease. Methods and results: Biopsy specimens from paediatric (<10years, n=14; >12years, n=15) and adult (n=27) IgAN showed a significant infiltrate of CD68+ macrophages. M2 macrophages, identified by CD163 or CD204 expression, were detected in glomeruli and the interstitium, being more prominent in adults versus young children. CD163+ and CD204+ macrophages were present in areas of fibrosis containing myofibroblasts, and double staining showed that CD163+ cells produced the profibrotic molecule, connective tissue growth factor. In young children, total CD68+ macrophages, but not M2 macrophages, correlated with glomerular hypercellularity. In contrast, in adults and older children, mesangial matrix expansion correlated with M2 macrophages but not with the total CD68+ macrophage infiltrate. Conclusions: Alternatively activated M2 macrophages are present in new-onset paediatric and adult IgAN, and this population may promote the development of fibrotic lesions.

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