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 alpha4beta7 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 alpha4 and beta7 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-alpha4 (TA-2), anti-beta7 or isotype-matched control antibodies. The initial mast cell hyperplasia in response to N. brasiliensis infection was significantly inhibited by either anti-alpha4 or anti-beta7 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-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 tongue tissue. These data suggest a role for alpha4 integrins, in particular alpha4beta7, in the regulation of mast cell precursor migration to the intestine.
Department of Pediatrics, Dalhousie University, Halifax, Canada.
T B
TB
Issekutz
A
A
Palecanda
U
U
Kadela-Stolarz
J S
JS
Marshall
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D004802:Eosinophilia / Q000469:parasitology; D006632:Histamine / Q000378:metabolism; D007073:Immunoglobulin E / Q000096:biosynthesis; D039001:Integrin alpha Chains; D039441:Integrin alpha4; D007421:Intestine, Small / Q000276:immunology / Q000469:parasitology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D008415:Mastocytosis / Q000469:parasitology* / Q000628:therapy; D009559:Nippostrongylus; D051381:Rats; D011917:Rats, Inbred Lew; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology / Q000628:therapy
D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039001:Integrin alpha Chains; C085725:integrin alpha7; D039441:Integrin alpha4; D007073:Immunoglobulin E; D006632:Histamine