The Hookworm Platelet Inhibitor

Functional Blockade of Integrins GPIIb/IIIa (αIIbβ3) and GPIa/IIa (α2β1) Inhibits Platelet Aggregation and Adhesion In Vitro

  • Chadderdon, Robert C.
  • Cappello, Michael

  • Departments of Pediatrics and Epidemiology and Public Health, Yale School of Medicine, New Haven, Connecticut

Reprints or correspondence: Dr. Michael Cappello, Dept. of Pediatrics, Yale School of Medicine, P.O. Box 208081, New Haven, CT 06520-8081 ([email protected]).

1Currently a student at Dartmouth Medical School, Hanover, NH.

Received 9 September 1998; revised 15 January 1999

All animal experiments were carried out under protocols approved by the Yale University Animal Care and Use Committee.

Grant support: NIH (AI-01299, HD-27757 to M.C.); American Heart Association (Grant-in-Aid to M.C.).

Journal of Infectious Diseases 179(5):p 1235-1241, May 1999. | DOI: 10.1086/314724

Hookworms, aggressive, blood-feeding, intestinal nematodes, are currently a leading cause of iron deficiency anemia in the developing world. An inhibitor of platelet aggregation and adhesion has been partially purified and characterized from soluble protein extracts of adultAncylostoma caninumhookworms. This protein, named the hookworm platelet inhibitor, has an estimated molecular mass of 15 kDa as determined by size-exclusion chromatography. In addition to blocking platelet aggregation in response to a variety of agonists, the partially purified inhibitor also prevents adhesion of resting platelets to immobilized fibrinogen and collagen. Inhibitory monoclonal antibodies were used to identify specific blockade of cell surface integrins GPIIb/IIIa (αIIbβ3) and GPIa/IIa (α2β1), the platelet receptors for fibrinogen and collagen, respectively. This broad-spectrum anti-platelet activity is also present in excretory and secretory products of adult worms, suggesting a biologic role for the hookworm platelet inhibitor in vivo.

Copyright © Copyright Oxford University Press 1999.