Abstract

The overall objectives of this research proposal are to study, by electron microscopy, 1) the composition of the junctions formed between the P. falciparum merozoite and erythrocyte membrane during merozoite invasion, 2) the formation of knobs on erythrocytes infected by P. falciparum or P. malariae, 3) the role of erythrocyte cytoskeleton in malaria and 4) the mode of action of cyclosporin A on the erythrocytic stages of P. falciparum. Immuno-electron microscopy using various monoclonals, protein-A gold and cryoultramicrotomy or LR White resin, will identify proteins and cytoskeleton which are associated with junctions formed between merozoites and erythrocyte membranes. The characterization of these junctions may reveal new approaches for inhibiting their formation, thereby helping to prevent malaria infection. Studies of knob formation and composition will give clues on how to inhibit their formation. This information may be helpful for preventing some complications of falciparum malaria, such as cerebral malaria. The understanding of the mode of action of cyclosporin A on the erythrocytic stages of P. falciparum will contribute to the advancement of our knowledge on the treatment of malaria. Thus, investigations proposed here should provide answers to a number of basic questions on host-parasite interaction and may lead to the discovery of better methods for the control of malaria.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI010645-18
Application #
3565441
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1978-09-29
Project End
1990-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
18
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Klotz, F W; Cohen, S J; Szarfman, A et al. (1996) Cross-reactive epitope among proteins in Plasmodium falciparum Maurer's clefts and primate leukocytes and platelets. Am J Trop Med Hyg 54:655-9
Alano, P; Read, D; Bruce, M et al. (1995) COS cell expression cloning of Pfg377, a Plasmodium falciparum gametocyte antigen associated with osmiophilic bodies. Mol Biochem Parasitol 74:143-56
Vernick, K D; Fujioka, H; Seeley, D C et al. (1995) Plasmodium gallinaceum: a refractory mechanism of ookinete killing in the mosquito, Anopheles gambiae. Exp Parasitol 80:583-95
Charoenvit, Y; Mellouk, S; Sedegah, M et al. (1995) Plasmodium yoelii: 17-kDa hepatic and erythrocytic stage protein is the target of an inhibitory monoclonal antibody. Exp Parasitol 80:419-29
Kaidoh, T; Nath, J; Fujioka, H et al. (1995) Effect and localization of trifluralin in Plasmodium falciparum gametocytes: an electron microscopic study. J Eukaryot Microbiol 42:61-4
Sam-Yellowe, T Y; Fujioka, H; Aikawa, M et al. (1995) Plasmodium falciparum rhoptry proteins of 140/130/110 kd (Rhop-H) are located in an electron lucent compartment in the neck of the rhoptries. J Eukaryot Microbiol 42:224-31
Shahabuddin, M; Kaidoh, T; Aikawa, M et al. (1995) Plasmodium gallinaceum: mosquito peritrophic matrix and the parasite-vector compatibility. Exp Parasitol 81:386-93
Bruce, M C; Carter, R N; Nakamura, K et al. (1994) Cellular location and temporal expression of the Plasmodium falciparum sexual stage antigen Pfs16. Mol Biochem Parasitol 65:11-22
Fujioka, H; Millet, P; Maeno, Y et al. (1994) A nonhuman primate model for human cerebral malaria: rhesus monkeys experimentally infected with Plasmodium fragile. Exp Parasitol 78:371-6
Maeno, Y; Fujioka, H; Hollingdale, M R et al. (1994) Ultrastructural localization of CD36 in human hepatic sinusoidal lining cells, hepatocytes, human hepatoma (HepG2-A16) cells, and C32 amelanotic melanoma cells. Exp Parasitol 79:383-90

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