The prototypic tissue pentraxin PTX3, in contrast to the short pentraxin serum amyloid P, inhibits phagocytosis of late apoptotic neutrophils by macrophages

André P. Van Rossum, Fausto Fazzini, Pieter C. Limburg, Angelo A. Manfredi, Patrizia Rovere-Querini, Alberto Mantovani, Cees G M Kallenberg

Research output: Contribution to journalArticle

Abstract

Objective. Phagocytosis of apoptotic cells can be facilitated by complement components and short pentraxins, such as serum amyloid P (SAP). In contrast, the long pentraxin PTX3 was shown to inhibit phagocytosis of apoptotic Jurkat cells by dendritic cells and to bind late apoptotic polymorphonuclear leukocytes (PMNs). Recently, levels of the pentraxin PTX3 were shown to parallel disease activity in small-vessel vasculitis, which is often characterized by leukocytoclasia, a persistence of leukocyte remnants in the vessel wall. We undertook this study to test our hypothesis that PTX3 inhibits phagocytosis of late apoptotic PMNs by macrophages, thereby leading to their accumulation in the vessel wall. Methods. Macrophages were allowed to phagocytose late apoptotic or secondary necrotic PMNs that were incubated with or without PTX3 for 30 minutes prior to phagocytosis. Phagocytosis was allowed to occur in the presence of 30% normal human serum with or without SAP and with or without depletion of complement. To discriminate between an inhibitory effect of PTX3 on binding and the internalization of apoptotic PMNs into macrophages, internalization was blocked by cytochalasin B. Results. SAP and complement were both necessary for effective in vitro phagocytosis. In contrast, PTX3 inhibited phagocytosis in a dose-dependent manner, from 11% inhibition at 6.25 μg/ml to almost complete inhibition at 100 μg/ml. Furthermore, PTX3 partly affected binding of apoptotic PMNs to macrophages. Conclusion. PTX3, in contrast to SAP and complement, inhibits phagocytosis of late apoptotic PMNs by monocyte-derived macrophages in a dose-dependent manner. Therefore, PTX3 can play a role in the development of leukocytoclasia by affecting the clearance of apoptotic PMNs, thereby inducing their accumulation in the vessel wall.

Original languageEnglish
Pages (from-to)2667-2674
Number of pages8
JournalArthritis and Rheumatism
Volume50
Issue number8
DOIs
Publication statusPublished - Aug 2004

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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