title: Adjuvant-free in vivo targeting. Antigen delivery by alpha 2-macroglobulin enhances antibody formation.
abstract: The proteinase "inhibitor" alpha 2-macroglobulin (alpha 2M) is able to entrap and form covalent linkages with diverse proteins during a transient proteinase-activated state. These complexes are rapidly endocytosed after binding to receptors present on macrophages and other cells. We have previously shown that compared to free hen egg lysozyme (HEL), alpha 2M-complexed HEL undergoes enhanced macrophage uptake, processing, and presentation to T hybridoma clones in vitro. Inasmuch as it is not clear whether T hybridoma responses accurately reflect primary immune responses in vivo, we studied antibody production in rabbits using two Ag complexed with either human alpha 2M (H alpha 2M) or a homologous protein purified from rabbit plasma, alpha 1-macroglobulin (R alpha 1M). Pathogen-free NZW rabbits received s.c. injections with adjuvant-free preparations of free HEL or porcine pancreatic elastase (PPE), H alpha 2M-HEL-PPE complexes, R alpha 1M-HEL-PPE complexes, or mixtures of the uncomplexed proteins. Complexing the Ag to alpha 2M resulted in 10 to 500-fold higher IgG titers compared to uncomplexed controls. Injection of Ag complexed to either H alpha 2M or R alpha 1M resulted in levels of anti-HEL IgG comparable to those elicited by emulsification in CFA. Inasmuch as inflammatory proteinases such as neutrophil elastase can initiate covalent complex formation with alpha 2M, we propose that "proteinase-activated" alpha 2M may mediate receptor-enhanced Ag uptake by macrophages, resulting in augmented Ag processing and antibody production.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: C T
authors.initials: CT
authors.lastname: Chu
authors.forename: T D
authors.initials: TD
authors.lastname: Oury
authors.forename: J J
authors.initials: JJ
authors.lastname: Enghild
authors.forename: S V
authors.initials: SV
authors.lastname: Pizzo
mesh_terms: D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D004705:Endocytosis; D007074:Immunoglobulin G / Q000096:biosynthesis; D009113:Muramidase / Q000276:immunology; D011817:Rabbits; D000511:alpha-Macroglobulins / Q000008:administration & dosage* / Q000502:physiology
chemical_list: D000941:Antigens; D007074:Immunoglobulin G; D000511:alpha-Macroglobulins; D009113:Muramidase