Blockade of either alpha-4 or beta-7 integrins selectively inhibits intestinal mast cell hyperplasia and worm expulsion in response to Nippostrongylus brasiliensis infection

Mast cells are known to express high levels of alpha4 integrins including a lpha4 beta7 and are found in increased numbers in mucosal inflammation. Mas t cell accumulation is particularly prominent in the intestine following ne matode infection. The adhesion molecule requirements for this process have not yet been defined. The role of alpha4 and beta7 integrin chains in the i ntestinal mast cell hyperplasia following infection of rats with the nemato de parasite Nippostrongylus brasiliensis was examined in this study. Rats w ere infected with N. brasiliensis larvae and treated with either anti-alpha 4 (TA-2), anti-beta7 or isotype-matched control antibodies. The initial mas t cell hyperplasia in response to N. brasiliensis infection was significant ly inhibited by either anti-alpha4 or anti-beta7 treatment. In contrast, th e intestinal eosinophil response to N. brasiliensis infection was not reduc ed at day 14 or day 16. Elevations in serum IgE levels due to N. brasiliens is infection were also not inhibited by anti-alpha4 or anti-beta7 antibody treatment. Anti-alpha4, antibody but not anti-beta7 antibody treatment also induced a small but significant decrease in the numbers of mast cells in t ongue tissue. These data suggest a role for alpha4 integrins, in particular alpha4 beta7, in the regulation of mast cell precursor migration to the in testine.