Prolonged somatostatin therapy may cause down-regulation of SSTR-like GPCRs on Schistosoma mansoni.

BACKGROUND & OBJECTIVES: Chemotherapy with praziquantel remains the only control measure to Schistosoma mansoni infections to date. The neuropeptide hormone somatostatin gives relief from gastrointestinal disturbances, liverpathology, and reduces egg production in S. mansoni infected mice, suggesting an interaction of somatostatin with the parasite rather than with the host alone. Using antibodies directed to epitopes of the seven somatostatin transmembrane receptors (SSTRs), the presence of SSTRs (or proteins that contain these epitopes) was shown on both worm- and egg-stages of S. mansoni. The present study was undertaken to investigate whether SSTRs on S. mansoni displayed homo/heterodimerisation properties as well as agonist induced down-regulation. RESULTS: Somatostatin therapy was effective after two days of treatment with no further reduction in pathology after five days of therapy. Immunohistochemistry performed on parasite sections showed reactivity of the anti-SSTR antibodies to the tegument and internal parts of adult S. mansoni worms. SDS-PAGE-Western blotting identified protein bands of 70-100 and 200-250 kDa molecular weight. Upon carboxymethylation of the sulfhydryl groups of proteins in the worm lysate, a reduction in density of the protein band at 200-250 kDa and an increase in density of the protein band at 70-100 kDa were noted. This suggested that a substantial amount of the proteins detected on the blot are present as a homo/heterodimer. A protein microarray was used to investigate whether somatostatin therapy induced receptor down- or up-regulation on the adult worm of S. mansoni. Slides spotted with primary anti-SSTR antibody were exposed to lysates of worms collected from infected C3H mice that received none, two days or five days somatostatin treatment, followed by a secondary anti-SSTR antibody coupled to a fluorophore. Comparison of the different samples in terms of parasite dilution till when the fluorescence was detectable, and the fluorescence intensity, proved that the proteins detected in the parasite worm have been down-regulated after five days of somatostatin treatment. CONCLUSION: SSTR-like GPCRs are being expressed by adult S. mansoni worms and extended somatostatin treatment may cause down-regulation of these receptors, thus reducing the therapeutic capacities of this neuropeptide. However, the presence of SSTRs on S. mansoni has not yet been proven on a genetic basis. Cross-reactivity of anti-SSTR antibodies with other G-protein coupled receptors (GPCR) thus cannot yet be excluded.

The distribution of interstitial cells of Cajal in the ileum is not altered by infection with Schistosoma mansoni.

BACKGROUND & OBJECTIVES: The interstitial cells of Cajal (ICC) act as pacemakers that generate slow waves and function as a relay between smooth muscle cells of the gastrointestinal (GI) tract. Recent reports indicate the crucial role played by the ICC in defining GI motility during human disease status like pyloric stenosis, Hirschsprung's disease and ulcerative colitis. Experimental data showed that Nippostrongylus infection in the rat caused an altered GI motility pattern accompanied by a complete loss of ICC-deep muscular plexus. The aim of the present study was to delineate if ICC were similarly affected during Schistosoma mansoni infections, thereby responsible for the disturbed GI motility patterns triggered in the afflicted mammalian host. METHODS & RESULTS: Immunohistochemistry was done using whole mounts and sections from naive and S. mansoni infected mice ileum. Primary antibodies detected Kit-immunoreactivity (Kit-ir representing ICC), PGP-9.5 (protein gene product 9.5 representing a neuronal marker), SK3 (ionic channel marker for non-Kit fibroblast like cells), and Cx43 (gap junction protein representing a muscle marker). Single/double immunofluorescence staining and confocal microscopy depicted that muscle thickness (Cx43-ir) and inflammatory infiltrate increased with infection. Kit-ir ICC and SK3-ir fibroblast like cells (FLC) were present at all normal locations as seen in controls and during acute and chronic stages of infection. INTERPRETATION & CONCLUSION: No disappearance of either ICC population was noted. A preferential (although not exclusive) location of inflammatory infiltrate in contact with SK3-ir FLC in the muscle layer was observed. The present study thus delineated that ICC are not affected during S. mansoni infections, and thereby may not be responsible for mediating the disturbed GI motility patterns caused by schistosomiasis.