RESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Antígenos CD/inmunología , Cadenas alfa de Integrinas , Mastocitosis/parasitología , Nippostrongylus , Infecciones por Strongylida/inmunología , Animales , Anticuerpos Antihelmínticos/biosíntesis , Eosinofilia/parasitología , Histamina/metabolismo , Inmunoglobulina E/biosíntesis , Integrina alfa4 , Intestino Delgado/inmunología , Intestino Delgado/parasitología , Pulmón/inmunología , Pulmón/metabolismo , Masculino , Mastocitosis/terapia , Ratas , Ratas Endogámicas Lew , Infecciones por Strongylida/parasitología , Infecciones por Strongylida/terapiaRESUMEN
The rat tapeworm, Hymenolepis diminuta, induces mastocytosis, hypertrophy of enteric smooth muscle, alteration of enteric myoelectric activity, and slowed enteric transit of the rat host's intestine. This report examines the resolution of both tapeworm-induced mastocytosis and tissue changes during the period following removal of the tapeworm with Praziquantel (PZQ). The dynamics of the mucosal mast cell (MMC) population following removal of the tapeworms was assessed by histochemical identification of MMC and morphometric techniques. As a possible mechanism of MMC population regulation, MMC apoptosis was examined over the same experimental period using the in situ nick end labeling of fragmented DNA (TUNEL). Shifts in MMC numbers were correlated with functional and morphological changes of the intestine following removal of the adult-stage tapeworm. Ileal tissues from rats infected 32 days with H. diminuta (the beginning of plateau phase of tapeworm-induced chronic mastocytosis) were harvested 1, 2, 3, and 4 weeks after the PZQ treatment. Control ilea were obtained either from rats which were never infected and never treated with PZQ or from rats infected with H. diminuta for 32 days but not treated with PZQ. In order to detect MMC and apoptosis, tissue sections of ileum were doubled stained sequentially with Astra blue for MMC granules followed by a modification of the TUNEL technique. No alteration in MMC numbers were observed in PZQ-treated animals until 3 weeks after the removal of the tapeworms. The decline of MMC occurred in the mucosa and submucosa. MMC numbers first approached uninfected control levels at 4 weeks posttreatment. Coincident with the decline in mucosal MMC numbers, the rate of MMC entering apoptosis also declined. Simultaneously, ileal smooth muscle layers, hypertrophied by infection, and mucosal structures began the process of involution and atrophy. Apoptosis of MMC in the submucosa and muscularis mucosa was not detected. In conclusion, H. diminuta-elicited mastocytosis and increased thickness of both mucosa and muscularis externa do not begin a decline toward control values until 3 weeks after the parasites are gone and normal intestinal motility is restored. These data are consistent with the lack of MMC mediation of altered motility, and the decline in the rate of MMC apoptosis at 3 weeks post-PZQ suggests that apoptosis may play an important role in the involution of tapeworm-induced mastocytosis.