Damage first; infect later
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《细胞学杂志》
Mota/Macmillan
Like a picky tourist looking for a hotel room, the malaria-causing protozoan Plasmodium passes through several cells before settling on one to infect. Margarida Carrolo, Maria Mota (Instituto Gulbenkian de Ciência, Oeiras, Portugal), and colleagues now report that the initial invasions cause the damaged cells to make a factor that primes other cells for infection.
The factor turned up in culture medium from infected or wounded cells. When added to uninfected cells, this conditioned medium doubled the level of infection. The factor was identified as hepatocyte growth factor (HGF), which is made by hepatocytes in response to wounding. Those cells that were permeable to dextran (because of Plasmodium-induced wounding) were the same ones that made HGF.
Mota earlier showed that the passage through cells primes Plasmodium for infection. Once it is primed, Plasmodium induces a folding of the plasma membrane that becomes a parasitophorous vacuole. The Portugese group noted HGF-induced changes in the actin cytoskeleton in hepatocytes, and they speculate that these changes may be necessary for early parasite development.
The HGF receptor Met is not a receptor for Plasmodium, but when the group inhibited Met's kinase activity this did prevent Plasmodium infection, even when the inhibition occurred after invasion. Any such treatment "needs to be prophylactic, because people don't know they are infected at this stage," says Mota. She is contacting companies that are developing anti-cancer drugs targeting Met, and also hopes to find other targets downstream of Met activation.
Reference:
Carrolo, M., et al. 2003. Nat. Med. 10.1038/nm947.(Damaged, dextrin-permeable cells (green))
Like a picky tourist looking for a hotel room, the malaria-causing protozoan Plasmodium passes through several cells before settling on one to infect. Margarida Carrolo, Maria Mota (Instituto Gulbenkian de Ciência, Oeiras, Portugal), and colleagues now report that the initial invasions cause the damaged cells to make a factor that primes other cells for infection.
The factor turned up in culture medium from infected or wounded cells. When added to uninfected cells, this conditioned medium doubled the level of infection. The factor was identified as hepatocyte growth factor (HGF), which is made by hepatocytes in response to wounding. Those cells that were permeable to dextran (because of Plasmodium-induced wounding) were the same ones that made HGF.
Mota earlier showed that the passage through cells primes Plasmodium for infection. Once it is primed, Plasmodium induces a folding of the plasma membrane that becomes a parasitophorous vacuole. The Portugese group noted HGF-induced changes in the actin cytoskeleton in hepatocytes, and they speculate that these changes may be necessary for early parasite development.
The HGF receptor Met is not a receptor for Plasmodium, but when the group inhibited Met's kinase activity this did prevent Plasmodium infection, even when the inhibition occurred after invasion. Any such treatment "needs to be prophylactic, because people don't know they are infected at this stage," says Mota. She is contacting companies that are developing anti-cancer drugs targeting Met, and also hopes to find other targets downstream of Met activation.
Reference:
Carrolo, M., et al. 2003. Nat. Med. 10.1038/nm947.(Damaged, dextrin-permeable cells (green))