Characterisation of alpha-1 giardin: an immunodominant Giardia lamblia annexin with glycosaminoglycan-binding activity.
Alpha-1 giardin is an immunodominant protein in the intestinal protozoan parasite Giardia lamblia. The Triage((R)) parasite panel, used to detect copro-antigens in stool from giardiasis patients, reacts with an epitope between amino acids 160 and 200 in alpha-1 giardin. This region of the protein is also highly immunogenic during human infections. Alpha-1 giardin is related to annexins and like many other annexins it was shown to be plasma membrane associated. Immunoelectron and immunofluorescence microscopy revealed that some alpha-1 giardin are displayed on the surface of recently excysted cells. Recombinant alpha-1 giardin displayed a Ca(2+)-dependent binding to glycosaminoglycans (GAGs), in particular heparan sulphate, a common GAG in the intestinal tract. Recombinant alpha-1 giardin bound to thin sections of human small intestine, a binding which could be inhibited by adding increasing concentrations of sulphated sugars. A surface associated trypsin activated Giardia lectin (taglin) has been suggested to be important for G. lamblia attachment. In this study we show that a monoclonal antibody that inhibits taglin recognises alpha-1 and alpha-2 giardin. Thus, alpha-1 giardin is a highly immunoreactive GAG-binding protein, which may play a key role in the parasite-host interaction. Our results further show a conserved function of annexins from lower to higher eukaryotes.
Weiland
Malin E-L
ME
Microbiology and Tumor Biology Center, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Palm
J E Daniel
JE
Griffiths
William J
WJ
McCaffery
J Michael
JM
Svärd
Staffan G
SG
D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis* / Q000378:metabolism; D016829:Giardia lamblia / Q000737:chemistry*; D005873:Giardiasis / Q000276:immunology* / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006790:Host-Parasite Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D033661:Oocysts / Q000737:chemistry*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism
D000953:Antigens, Protozoan; D006497:Heparan Sulfate; D011994:Recombinant Proteins