Local macrophage proliferation in experimental Goodpasture's syndrome

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Abstract

Summary: The traditional dogma that macrophages do not proliferate within inflammatory lesions has recently been challenged. We have addressed this issue in a study of experimental Goodpasture's syndrome (rat anti‐glomerular basement membrane [GBM] disease). Monocyte and macrophage proliferation was assessed during the initation and evolution of this severe inflammatory disease by expression of the proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation using twocolour immunohistochemistry. This study found that: (i) the initial accumulation of ED1+ macrophages in the kiney and lung seen during the indcution of disease resulted from blood monocyte recruitment; however, large numbers of proliferating macrophages (up to 60% of total macrophages) were present in these tissues during subsequent disease evolution; (ii) macrophage proliferation was restricted to the kidney and lung as demonstrated by the complete lack of PCNA expression and BrdU uptake by circulating monocytes and unchanged levels of resident macrophage proliferation within the spleen and liver; (iii) local macrophage proliferation within inflamed tissues was confined to cells of an ED1+ED2ED3 phenotype indicating that they were recently arrived monocytres and not resident tissue macrophages; and (iv) proliferating macrophages within inflamed tissues were localized in focal areas of severe tissue damage. In conclusion, this study has demonstrated that local proliferation of recuited monocytes makes a major contribution to macrophage accumulation within inflamed tissues during the evolution of rat anti‐GBM disease. Furthermore, local macrophage proliferation may play an important role in the mediation of tissue injury in this disease model.

Original languageEnglish
Pages (from-to)151-156
Number of pages6
JournalNephrology
Volume1
Issue number2
DOIs
Publication statusPublished - 1 Jan 1995
Externally publishedYes

Keywords

  • Goodpasture's syndrome
  • immunohistochemistry
  • inflammation
  • macrophage
  • PCNA
  • proliferation

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