Trichinella spiralis: vascular endothelial growth factor is up-regulated within the nurse cell during the early phase of its formation.

The L1 larval stage of Trichinella spiralis induces modification in a portion of striated skeletal muscle cell resulting in the formation of the nurse cell. This specialized host cell is completely encased in a capsule composed mainly of collagen type IV and type VI, which, in turn, is surrounded by a unique rete of vessels whose formation begins on around day 12 after intracellular infection. We investigated the possibility that vascular endothelial growth factor (VEGF) may be up-regulated during nurse cell formation by employing immunohistochemistry and in situ hybridization on synchronously infected mouse muscle tissue. Both VEGF mRNA and VEGF peptide were detected in the developing nurse cell cytoplasm from day 7 up to 16 mo after infection. In addition, VEGF was also detected in cells in the area immediately surrounding the nurse cell on days 15 and 17. On the basis of these results, we propose that hypoxia is induced by T. spiralis within the developing nurse cell some time prior to the up-regulation of VEGF, perhaps as early as day 7. We further propose, on the basis of the continued presence of VEGF in nurse cell cytoplasm, that a constant state of hypoxia cell is maintained.

Trichinella spiralis: synthesis of type IV and type VI collagen during nurse cell formation.

The portion of skeletal muscle fiber (Nurse cell) harboring Trichinella spiralis is surrounded by an acellular capsule susceptible to digestion with collagenase. Antibodies recognized type IV and type VI collagen in the capsule, while the periodic acid Schiff reagent stained the capsule differentially, revealing at least two distinct layers. RNA analysis showed that mRNA specific for type IV and type VI collagen was present in muscle tissue on Days 9 and 15, but not on Day 3, following intracellular infection. In situ hybridization showed that most of the mRNA for both types was within the Nurse cell, and all enlarged Nurse cell nuclei were transcriptionally active for those messages. Synthesis of type IV collagen mRNA was absent by Day 24. In contrast, type VI collagen mRNA was still present at 24 days and 8 months. These results support the hypothesis that T. spiralis, either directly or indirectly, influences the synthesis of these two collagen types throughout its own developmental cycle in the Nurse cell.