Effects of Helicobacter suis γ-glutamyl transpeptidase on lymphocytes: modulation by glutamine and glutathione supplementation and outer membrane vesicles as a putative delivery route of the enzyme

Helicobacter (H.) suis colonizes the stomach of the majority of pigs as well as a minority of humans worldwide. Infection causes chronic inflammation in the stomach of the host, however without an effective clearance of the bacteria. Currently, no information is available about possible mechanisms H. suis utilizes to interfere with the host immune response. This study describes the effect on various lymphocytes of the γ-glutamyl transpeptidase (GGT) from H. suis. Compared to whole cell lysate from wild-type H. suis, lysate from a H. suis ggt mutant strain showed a decrease of the capacity to inhibit Jurkat T cell proliferation. Incubation of Jurkat T cells with recombinantly expressed H. suis GGT resulted in an impaired proliferation, and cell death was shown to be involved. A similar but more pronounced inhibitory effect was also seen on primary murine CD4+ T cells, CD8+ T cells, and CD19+ B cells. Supplementation with known GGT substrates was able to modulate the observed effects. Glutamine restored normal proliferation of the cells, whereas supplementation with reduced glutathione strengthened the H. suis GGT-mediated inhibition of proliferation. H. suis GGT treatment abolished secretion of IL-4 and IL-17 by CD4+ T cells, without affecting secretion of IFN-γ. Finally, H. suis outer membrane vesicles (OMV) were identified as a possible delivery route of H. suis GGT to lymphocytes residing in the deeper mucosal layers. Thus far, this study is the first to report that the effects on lymphocytes of this enzyme, not only important for H. suis metabolism but also for that of other Helicobacter species, depend on the degradation of two specific substrates: glutamine and reduced glutatione. This will provide new insights into the pathogenic mechanisms of H. suis infection in particular and infection with gastric helicobacters in general

In vitro validation and reliability study of electromagnetic skin sensors for evaluation of end range of motion positions of the hip

There is growing evidence that femoroacetabular impingement (FAI) is a probable risk factor for the development of early osteoarthritis in the nondysplastic hip. As FAI arises with end range of motion activities, measurement errors related to skin movement might be higher than anticipated when using previously reported methods for kinematic evaluation of the hip. We performed an in vitro validation and reliability study of a noninvasive method to define pelvic and femur positions in end range of motion activities of the hip using an electromagnetic tracking device. Motion data, collected from sensors attached to the bone and skin of 11 cadaver hips, were simultaneously obtained and compared in a global reference frame. Motion data were then transposed in the hip joint local coordinate systems. Observer-related variability in locating the anatomical landmarks required to define the local coordinate system and variability of determining the hip joint center was evaluated. Angular root mean square (RMS) differences between the bony and skin sensors averaged 3.2A degrees (SD 3.5A degrees) and 1.8A degrees (SD 2.3A degrees) in the global reference frame for the femur and pelvic sensors, respectively. Angular RMS differences between the bony and skin sensors in the hip joint local coordinate systems ranged at end range of motion and dependent on the motion under investigation from 1.91 to 5.81A degrees. The presented protocol for evaluation of hip motion seems to be suited for the 3-D description of motion relevant to the experimental and clinical evaluation of femoroacetabular impingement