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 α4 integrins including α4β7 and are found in increased numbers in mucosal inflammation. Mast cell accumulation is particularly prominent in the intestine following nematode infection. The adhesion molecule requirements for this process have not yet been defined. The role of α4 and β7 integrin chains in the intestinal mast cell hyperplasia following infection of rats with the nematode parasite Nippostrongylus brasiliensis was examined in this study. Rats were infected with N. brasiliensis larvae and treated with either anti-α4 (TA-2), anti-β7 or isotype-matched control antibodies. The initial mast cell hyperplasia in response to N. brasiliensis infection was significantly inhibited by either anti-α4 or anti-β7 treatment. In contrast, the intestinal eosinophil response to N. brasiliensis infection was not reduced at day 14 or day 16. Elevations in serum IgE levels due to N. brasiliensis infection were also not inhibited by anti-α4 or anti-β7 antibody treatment. Anti-α4 antibody but not anti-β7 antibody treatment also induced a small but significant decrease in the numbers of mast cells in tongue tissue. These data suggest a role for α4 integrins, in particular α4β7, in the regulation of mast cell precursor migration to the intestine.