BB-10010, an analogue of macrophage inflammatory protein-1 alpha, reduces proliferation in murine small-intestinal crypts

Background: The small-intestinal epithelium, a rapidly proliferating tissue , is highly sensitive to cycle-specific agents such as radiation. Macrophag e inflammatory protein (MIP)-1 alpha has been shown to reduce cell prolifer ation in bone marrow, seminiferous epithelium, and skin. The current work i nvestigates the activity of an MIP-1 alpha variant, BB-10010, in the gut. M ethods: A single dose of either 0.4 mu g/kg or 200 mu g/kg was administered to mice 2, 4, 6, 8, 10, 12, or 14 h before animal death. Fifteen crypts fr om the midpoint of the small intestine were dissected from each animal and squashed, and the numbers of vincristine-arrested metaphases was counted fo r each fifth of the crypts. Results: A 40 %-50 % reduction of accumulated m etaphases throughout all crypt segments was observed in animals injected wi th 200 mu g/kg of BB-10010 2 h and 4 h before death (P < 0.0001). The anima ls that received 0.4 mu g/kg showed a similar effect at 4 h (P < 0.0001). C onclusions: The results provide evidence of a significant reduction in numb ers of intestinal cryptal cells passing through mitosis at specific time pe riods after a single administration of BB-10010. By putting these cells tem porarily out of the mitotic phase of the cell cycle this protein might redu ce the side effects of radiation therapy to patients undergoing abdominal o r pelvic treatments.