Human hololactoferrin: endocytosis and use as an iron source by the parasite Entamoeba histolytica.
Entamoeba histolytica is an enteric protozoan that exclusively infects human beings. This parasite requires iron for its metabolic functions. Lactoferrin is a mammalian glycoprotein that chelates extracellular iron on mucosal surfaces, including the surface of the large intestine, where E. histolytica initiates infection. This work examined the interaction in vitro of E. histolytica trophozoites with human hololactoferrin (iron-saturated lactoferrin). A minimum concentration of 50 microM Fe from hololactoferrin supported growth of the amoeba. Amoebic binding sites for hololactoferrin were different from those for human apolactoferrin, holotransferrin and haemoglobin. One amoebic hololactoferrrin-binding polypeptide of 90 kDa was found, which was not observed after treatment of trophozoites with trypsin. Hololactoferrin-binding-protein levels increased in amoebas starved of iron, or grown in hololactoferrin. Internalization of hololactoferrin was inhibited by filipin. Endocytosed hololactoferrin colocalized with an anti-chick embryo caveolin mAb in amoebic vesicles, and lactoferrin was further detected in acidic vesicles; amoebic caveolin of 22 kDa was detected by Western blotting using this antibody. Cysteine proteases from amoebic extracts were able to cleave hololactoferrin. Together, these data indicate that E. histolytica trophozoites bind to hololactoferrin through specific membrane lactoferrin-binding proteins. This ferric protein might be internalized via caveolae-like microdomains, then used as an iron source, and degraded.
León-Sicairos
Nidia
N
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. 14-740, México, D F 07000, Mexico.
Reyes-López
Magda
M
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. 14-740, México, D F 07000, Mexico.
Canizalez-Román
Adrián
A
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. 14-740, México, D F 07000, Mexico.
Bermúdez-Cruz
Rosa María
RM
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. 14-740, México, D F 07000, Mexico.
Serrano-Luna
Jesús
J
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. 14-740, México, D F 07000, Mexico.
Arroyo
Rossana
R
Departamento de Patología Experimental, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. 14-740, México, D F 07000, Mexico.
de la Garza
Mireya
M
Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, Apdo. 14-740, México, D F 07000, Mexico.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000913:Antibodies, Protozoan / Q000276:immunology*; D004705:Endocytosis / Q000502:physiology*; D004748:Entamoeba histolytica / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins; D007781:Lactoferrin / Q000378:metabolism*; D033863:Transferrin-Binding Proteins
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D033862:Iron-Binding Proteins; D033863:Transferrin-Binding Proteins; C492629:hololactoferrin, human; D007501:Iron; D007781:Lactoferrin