Alpha-2-macroglobulin receptor is differently expressed in peritoneal macrophages from C3H and C57/B16 mice and up-regulated during Trypanosoma cruzi infection.
Chagas' disease is caused by the protozoan Trypanosoma cruzi. The acute phase of T. cruzi infection, which can be conveniently studied in mouse models, is thought to be a determinant of survival and of the pathological features of the chronic phase. With regard to the occurrence of early death and parasitaemia levels C3H and C57/B16 mice are classically classified as 'susceptible' and 'resistant' to T. cruzi infection, respectively. Alpha-2-macroglobulin (A2M) is a physiological proteinase inhibitor found in tissues and in the plasma of mammals. Previous studies showed that A2M plasma levels increase in C3H mice acutely infected by T. cruzi but do not change in C57/B16 mice. This difference might involve two possible phenomena, concerning A2M synthesis and/or clearance by its receptor (A2M-R). In this study, we examined by flow cytometry the binding of A2M-trypsin conjugated with FITC to macrophages from normal and T. cruzi-infected C3H and C57/B16 mice. Our present results show for the first time that A2M-R is expressed more (by approximately 33%) in the surface of cells from normal C57/B16 as compared to C3H mice. We also show that A2M-R expression is up-regulated in both strains during acute T. cruzi infection, but at higher levels and earlier in C57/B16 mice. At the same time, peritoneal cells become activated as judged by: (1) increase of their size and granularity; (2) gradual increase of Fc gamma RII/III expression assayed by 2.4G2 binding; (3) down-modulation of F4/80 binding, a mAb that recognizes an antigen typically expressed in resident macrophages. Finally, our results indicate that as macrophages become activated in vivo a higher expression of A2M-R is observed.
Coutinho
C M
CM
Lab. Biologia Celular, DUBC, Instituto-Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil. claudia@gene.dbbm.fiocruz.br
Cavalcanti
G
G
DaMatta
R A
RA
Van Leuven
F
F
Araújo-Jorge
T C
TC
D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D014355:Chagas Disease / Q000378:metabolism*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D007700:Kinetics; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000378:metabolism / Q000469:parasitology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000032:analysis / Q000096:biosynthesis*; D013045:Species Specificity; D014349:Trypanosoma cruzi; D015854:Up-Regulation / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000032:analysis / Q000096:biosynthesis
D005456:Fluorescent Dyes; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000511:alpha-Macroglobulins; D016650:Fluorescein-5-isothiocyanate