App1: an antiphagocytic protein that binds to complement receptors 3 and 2.
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.
Stano
Paola
P
Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425.
Williams
Virginia
V
Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425.
Villani
Maristella
M
Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425.
Cymbalyuk
Eugene S
ES
Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425.
Qureshi
Asfia
A
Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425.
Huang
Yuxiang
Y
Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425.
Morace
Giulia
G
Dipartimento di Sanita' Pubblica, Microbiologia-Virologia, Universita' degli Studi di Milano, Milan, Italy.
Luberto
Chiara
C
Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425.
Tomlinson
Stephen
S
Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425.
Del Poeta
Maurizio
M
Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425.|Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425.|Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC 29425.
D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D016466:CHO Cells; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000472:pathogenicity*; D005656:Fungal Proteins / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D017464:Receptors, Complement 3d / Q000378:metabolism*
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; C535050:App1 protein, Cryptococcus neoformans; D002352:Carrier Proteins; D005656:Fungal Proteins; D016177:Macrophage-1 Antigen; D017464:Receptors, Complement 3d