Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59.
Exosomes are secreted nanometer-sized vesicles derived from antigen-presenting cells, which have attracted recent interest as they likely play important roles in immune regulation, and their use as cell-free tools for immunotherapy has been proposed. Liposomes used clinically as transport vehicles can activate the complement system, leading to their rapid degradation and significant inflammatory toxicity. The use of isolated exosomes in therapy, therefore, may also elicit complement activation, reducing their potential efficacy. We have examined the expression and functional roles of the membrane regulators of complement (CD46, CD55 and CD59) on antigen-presenting cell-derived exosomes. Exosomes express the glycosylphosphatidylinositol (GPI)-anchored regulators CD55 and CD59, but not the transmembrane protein CD46. Antibody blocking of CD55 in the presence of sensitizing antibody (w6/32) and human serum resulted in increased C3b deposition and significantly increased exosome lysis. Blockade of CD59 also resulted in significant lysis, while blocking both CD55 and CD59 increased lysis still further. We conclude that exosomes express GPI-anchored complement regulators in order to permit their survival in the extracellular environment.
Clayton
Aled
A
Section of Clinical Oncology and Palliative Medicine, Department of Medicine, University of Wales College of Medicine, Velindre Hospital, Whitchurch, Cardiff, GB. aled.Clayton@velindre-tr.wales.nhs.uk
Harris
Claire L
CL
Court
Jacquelyn
J
Mason
Malcolm D
MD
Morgan
B Paul
BP
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D018958:CD55 Antigens / Q000276:immunology*; D018957:CD59 Antigens / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000276:immunology; D003167:Complement Activation; D003179:Complement C3b / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis; D009000:Monocytes / Q000166:cytology; D015388:Organelles / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D005452:Fluoresceins; D005456:Fluorescent Dyes; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; C085925:calcein AM; D003179:Complement C3b; D003165:Complement System Proteins