Different patterns of the L-histidine decarboxylase (HDC) gene expression in mice resistant and susceptible to experimental cutaneous leishmaniasis

Objective and design: In the present study the experimental murine Leishmania major (L. major) infection model was used to investigate the role of histamine biosynthesis in cutaneous leishmaniasis.Subjects, treatment and methods: A novel RNase Protection Assay (RPA) was developed and applied for the assessment of L-histidine decarboxylase (HDC) gene expression in organs of resistant C57BL/6 and susceptible BALB/c mice after infection with L. major.Results: In the acute phase of infection a rapid but transient induction of HDC expression was observed in the infected lymph nodes of both strains correlating both temporally and spatially with parasite spread. The signal was present in the draining popliteal lymph nodes of both hosts, however, only susceptible mice known to be unable to control parasite dissemination showed induction of HDC in their distant periaortic lymph nodes as well. During the chronic phase of infection only the heavily parasitized organs of BALB/c mice showed high HDC gene expression.Conclusions: These data suggest that expression of the histamine-producing enzyme HDC in the decisive acute phase of leishmaniasis is not coupled with development of either appropriate Th1 or inadequate Th2 responses to L. major. We hypothesize however, that during the chronic phase of infection elevated HDC levels, possibly of mast cell origin, are associated with Th2-dominated responses and serious disease development.Received 12 May 2003; returned for revision 3 July 2003; returned for final revision 11 September 2003; accepted by M. Parnham 24 September 2003     

Ultrastructural immunolocalization of bone sialoprotein in guinea-pig osteoarthritis

In diarthrodial joints, bone and cartilage are structurally and functionally inseparable as shown in osteoarthritis (OA), where subchondral bone changes are integral in the disease process. By ultrastructural immunohistochemistry using polyclonal antibodies against guinea-pig bone sialoprotein (BSP), we investigated the distribution of this matrix protein at the osteocartilaginous interface in Hartley guinea-pig knees at different stages of primary osteoarthritis. Between 6 and 12 months they developed moderate osteoarthritic changes predominantly in the medial condyle, progressing to severe OA at 30 months. In all age groups BSP labeling was concentrated to the osteocartilaginous interface at a 1 μm narrow zone at the interface. In the medial osteoarthritic condyle, BSP was increased as compared with the lateral nonosteoarthritic condyle, but only at 30 months, when cartilage fibrillation correlated to BSP. Our observations suggest that altered BSP abundance may be a potential bone marker for late stage OA, while early events in bone cannot be monitored. BSP is expressed early in osteogenesis and may have a role in biological mineralization and growth. Since a sharp zone of intense BSP labeling remains at a remarkably constant level throughout life in guinea-pigs, BSP may have an important structural and/or regulating role at the interface. The protein may act as an anchor of calcified articular cartilage to subchondral bone or by regulating mineralization at the osteocartilaginous interface.