Macrophages from human lymphoma patients cause mouse lymphoma in mice, UCSF study finds

UCSF researchers have found that macrophages--literally "big eaters," normally key immune defense cells that engulf and devour bacteria and tumor cells--when taken from HIV-infected lymphoma patients and injected into mice, induced aggressive mouse T-cell lymphomas in the mice. Macrophages from healthy donors did not.

"This research establishes that macrophages can cause disease as opposed to current dogma which asserts that the purpose of these cells is benevolent, solely to assist in fighting disease," said the study's lead investigator, Michael S. McGrath, MD, PhD, UCSF professor of laboratory medicine at UCSF's Positive Health Program at San Francisco General Hospital Medical Center (SFGHMC). The study is published in the October issue of Cancer Research.

Researchers used SCID (severe combined immunodeficiency disease) mice that lack functional T and B lymphocytes and are used for the study of human lymphoid tissues. They injected mice with tumor cells--some with macrophages and lymphoma cells together, some with macrophages separately, and some with lymphoma cells separately--from HIV-infected patients with a rare form of non-Hodgkin's lymphoma. They also injected some mice with normal human macrophages from healthy subjects.

"Most scientists believe that the macrophages present in tumors are there to help fight the cancer," said McGrath.

The mice injected with both macrophages and lymphoma cells from the HIV-infected lymphoma patients and mice injected with only the macrophages (separated from the lymphoma cells) from the HIV-infected lymphoma patients developed lymphomas.

None of the mice injected with just the lymphoma T-cells from the HIV-infected lymphoma patients and none of the mice injected with normal human macrophages from healthy subjects developed lymphomas.

"Our theory is that, during HIV infection, disease associated macrophages have HIV inserted near growth promoting genes allowing macrophages

Contact: Jeff Sheehy
University of California - San Francisco

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