Calcium-dependent proapoptotic effect of Taenia solium metacestodes annexin B1 on human eosinophils: a novel strategy to prevent host immune response.
Annexins are a family of calcium-dependent phospholipid-binding proteins that have been proposed to be involved in a wide range of important biological processes. At present, only a few annexins have been identified in parasites, and the physiological roles of these annexins are obscure. Earlier, we cloned a novel annexin (annexin B1) from Taenia solium metacestodes and found that annexin B1 was detectable in the surrounding host-derived layer with granulomaous infiltration. The objective of this study was to investigate the secretion and physiological function of annexin B1. We expressed a green fluorescent protein-tagged annexin B1 (GFP-anxB1) in living SiHa cells and showed that it was secreted upon stimulation with dexamethasone (Dex). This secretion was not inhibited by brefeldin A but was blocked by pre-treatment with the intracellular calcium-specific chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Furthermore, we describe for the first time that annexin B1 can bind to the extracellular surface of human eosinophils and produce Ca(2+)-influx. The Ca(2+)-influx induced apoptosis in eosinophils, which was inhibited by pre-loading the Ca(2+) channel blocker 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-metho-xyphenethyl]-1H-imidazole, HCl (SKF-96365). In conclusion, these findings represent direct and substantial evidence for the secretion of annexin B1 by living cells; the apoptosis in eosinophil induced by annexin B1 might be a novel strategy for T. solium metacestodes to prevent the host's immune attack.
Yan
Hong-Li
HL
Institute of Medical Genetics, Second Military Medical University, Shanghai 200433, PR China.
Xue
Geng
G
Mei
Qian
Q
Ding
Fei-Xiang
FX
Wang
Yu-Zhao
YZ
Sun
Shu-Han
SH
D000818:Animals; D017302:Annexins / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020126:Brefeldin A / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D045304:Cytochromes c / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D005089:Exocytosis / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D008954:Models, Biological; D011485:Protein Binding / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D041201:Taenia solium / Q000378:metabolism*
D017302:Annexins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D020126:Brefeldin A; D000001:Calcimycin; D003907:Dexamethasone; D045304:Cytochromes c; D053148:Caspase 3; D002118:Calcium