In previous studies, we showed that the pathogenic fungus Cryptococcus neoformans (Cn) produces a specific and unique protein called antiphagocytic protein 1 (App1), which inhibits phagocytosis of Cn by alveolar macrophages (AMs). Phagocytosis of Cn by AMs occurs mainly through a complement- or Ab-mediated mechanism. Among AM receptors, complement receptor 3 (CR3) and FcRgamma are the most common receptors involved in the phagocytic process. Because App1 inhibits phagocytosis of complement- but not Ab-coated erythrocytes, we investigated the role of CR3 in App1-macrophage interactions. We found that App1 binds to CR3 and if CR3 is absent from the surface of AMs, its antiphagocytic action is lost. When we investigated whether App1 would also bind to other complement receptor(s), we found that App1 does bind to complement receptor 2 (CR2) in a dose-dependent manner. In certain lymphoma cell lines, cellular proliferation is stimulated by complement through CR2, providing a potential use of App1 as a proliferation inhibitor of these cells. Initially discovered as an antiphagocytic protein regulating CR3-mediated innate immunity, App1 may also play a key role in the regulation of acquired immunity, because CR2 is mainly localized on B cells.

App1: an antiphagocytic protein that binds to complement receptors 3 and 2 / P. Stano, V. Williams, M. Villani, E.S. Cymbalyuk, A. Qureshi, Y. Huang, G. Morace, C. Luberto, S. Tomlinson, M. Del Poeta. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 182:1(2009 Jan 01), pp. 84-91. [10.4049/jimmunol.182.1.84]

App1: an antiphagocytic protein that binds to complement receptors 3 and 2

P. Stano
Primo
;
G. Morace;
2009

Abstract

In previous studies, we showed that the pathogenic fungus Cryptococcus neoformans (Cn) produces a specific and unique protein called antiphagocytic protein 1 (App1), which inhibits phagocytosis of Cn by alveolar macrophages (AMs). Phagocytosis of Cn by AMs occurs mainly through a complement- or Ab-mediated mechanism. Among AM receptors, complement receptor 3 (CR3) and FcRgamma are the most common receptors involved in the phagocytic process. Because App1 inhibits phagocytosis of complement- but not Ab-coated erythrocytes, we investigated the role of CR3 in App1-macrophage interactions. We found that App1 binds to CR3 and if CR3 is absent from the surface of AMs, its antiphagocytic action is lost. When we investigated whether App1 would also bind to other complement receptor(s), we found that App1 does bind to complement receptor 2 (CR2) in a dose-dependent manner. In certain lymphoma cell lines, cellular proliferation is stimulated by complement through CR2, providing a potential use of App1 as a proliferation inhibitor of these cells. Initially discovered as an antiphagocytic protein regulating CR3-mediated innate immunity, App1 may also play a key role in the regulation of acquired immunity, because CR2 is mainly localized on B cells.
English
Settore MED/07 - Microbiologia e Microbiologia Clinica
Articolo
Esperti anonimi
Pubblicazione scientifica
1-gen-2009
American Association of Immunologists
182
1
84
91
8
Pubblicato
Periodico con rilevanza internazionale
Aderisco
info:eu-repo/semantics/article
App1: an antiphagocytic protein that binds to complement receptors 3 and 2 / P. Stano, V. Williams, M. Villani, E.S. Cymbalyuk, A. Qureshi, Y. Huang, G. Morace, C. Luberto, S. Tomlinson, M. Del Poeta. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 182:1(2009 Jan 01), pp. 84-91. [10.4049/jimmunol.182.1.84]
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Article (author)
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P. Stano, V. Williams, M. Villani, E.S. Cymbalyuk, A. Qureshi, Y. Huang, G. Morace, C. Luberto, S. Tomlinson, M. Del Poeta
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/47629
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