Rickettsia rickettsii Infection of Human Macrovascular and Microvascular Endothelial Cells Reveals Activation of Both Common and Cell Type-Specific Host Response Mechanisms▿

Although inflammation and altered barrier functions of the vasculature, due predominantly to the infection of endothelial cell lining of small and medium-sized blood vessels, represent salient pathological features of human rickettsioses, the interactions between pathogenic rickettsiae and microvascular endothelial cells remain poorly understood. We have investigated the activation of nuclear transcription factor-kappa B (NF-κB) and p38 mitogen-activated protein (MAP) kinase, expression of heme oxygenase 1 (HO-1) and cyclooxygenase 2 (COX-2), and secretion of chemokines and prostaglandins after Rickettsia rickettsii infection of human cerebral, dermal, and pulmonary microvascular endothelial cells in comparison with pulmonary artery cells of macrovascular origin. NF-κB and p38 kinase activation and increased HO-1 mRNA expression were clearly evident in all cell types, along with relatively similar susceptibility to R. rickettsii infection in vitro but considerable variations in the intensities/kinetics of the aforementioned host responses. As expected, the overall activation profiles of macrovascular endothelial cells derived from human pulmonary artery and umbilical vein were nearly identical. Interestingly, cerebral endothelial cells displayed a marked refractoriness in chemokine production and secretion, while all other cell types secreted various levels of interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in response to infection. A unique feature of all microvascular endothelial cells was the lack of induced COX-2 expression and resultant inability to secrete prostaglandin E2 after R. rickettsii infection. Comparative evaluation thus yields the first experimental evidence for the activation of both common and unique cell type-specific host response mechanisms in macrovascular and microvascular endothelial cells infected with R. rickettsii, a prototypical species known to cause Rocky Mountain spotted fever in humans

Evaluation of peripheral nerve regeneration in Murphy Roths Large mouse strain following transection injury.

Aim: Murphy Roths Large (MRL/MpJ) mice have demonstrated the ability to heal with minimal or no scar formation in several tissue types. In order to identify a novel animal model, this study sought to evaluate whether this attribute applies to peripheral nerve regeneration. Materials & methods: This was a two-phase study. 6-week-old male mice were divided into two interventional groups: nerve repair and nerve graft. The MRL/MpJ was compared with the C57BL/6J strain for evaluation of both functional and histological outcomes. Results: MRL/MpJ strain demonstrated superior axon myelination and less scar formation, however functional outcomes did not show significant difference between strains. Conclusion: Superior histological outcomes did not translate into superior peripheral nerve regeneration in MRL/MpJ strain