Blockade of integrin α4β7 selectively inhibits intestinal mast cell hyperplasia in nippostrongylus brasiliensis infected rats

The effects of an antibody to rat β7 (TA-6) on the mucosal response to infection with the nematode parasite Nippostrongylus brasiliensis were examined and compared with those of an anti-α4 antibody (TA-2) or a control antibody (B9). Groups of 4 male Lewis rats were infected with 1500 L₃ Nb larvae, injected with 2mg of TA-2, TA-6 or B9 on days 2, 4 and 8 post infection and examined at day 16. Mast cell counts per 100 fields were assessed in Toluidine blue stained gut tissue sections. A significant (p<0.01) decrease in duodenal mast cell numbers was observed in rats treated with either antiβ7 (772 +/-148) or anti-α4 (715 +/- 167) when compared with infected animals treated with control antibody (2304 +/- 475). Similar changes were observed in tissue histamine content. In contrast, neither β7 nor α4 blockade had any significant effect on the parasite induced rise in duodenal eosinophil numbers. At day 14, both anti-β7 and anti-α4 treated groups had an increased worm burden (P<0.01 and P<0.05 respectively). While only anti-β7 significantly increased worm burden by day 16. Total serum IgE levels were elevated in all the animals and similar, in the three antibody treated groups, on both days 14 or 16 post infection. These findings suggest a key role for α4β7 in intestinal mast cell hyperplasia. However, eosinophil accumulation and the IgE response were α4β7 independent.