Four days later, monocytes could not be detected in the brains of any of the 15 mice that were pre-treated with LPS and then injected with normal monocytes producing GFP alone. By contrast, monocytes were readily detected in the brains of about 25% of mice pre-treated with LPS and then injected with HIV-and-GFP-producing monocytes.
"Clearly, HIV-infected monocytes uniquely benefit from the LPS that is present in high amounts in the blood of HIV-infected people," says Dr. Goldstein. "So when HIV-infected monocytes are 'knocking on the door' of the BBB and starting to crack it open, the LPS facilitates their entry by making the BBB more permeable, apparently by weakening blood vessel structure."
If HIV-infected monocytes and LPS in the bloodstream can be considered a one-two punch for entry into the brain, a third punchsimply having a systemic HIV infectionalso seems to help soften up the BBB. In making this discovery, Dr. Goldstein used his HIV-TG mouse strain, in which HIV is known to replicate inside brain cells associated with the BBB. These HIV-TG mice, along with control mice, were injected with LPS and, three hours later, intravenously injected with HIV-and-GFP-producing monocytes from the HIV/GFP-TG mouse strain.
Four days later, HIV-producing monocytes could be detected in the brains of about 25 percent of the control mice, as in the preceding experiment. By contrast, more than twice as many (70 percent) of the brains of HIV-TG mice that support systemic HIV infection contained HIV-producing monocytes. Even more impressive: When present, HIV-producing monocytes were three times more numerous in the brains of HIV-TG mice than in the brains of control mice.
"These results demonstrate very dramatically that HIV infection of cells associated with the BBB, in conjunction with LPS exposure, contributes to BBB breakdown,"
|Contact: Michael Heller|
Albert Einstein College of Medicine