Nitric oxide as a mediator of increased microvascular permeability during acute rickettsioses.
Rickettsiae primarily infect the microvascular endothelium, leading to changes in microvascular permeability that result in potentially severe pulmonary and cerebral edema. The mechanisms responsible for these changes are not well understood. One potential mechanism of increased vascular permeability is the anti-rickettsial nitric oxide response described by Walker and colleagues. We hypothesized that anti-rickettsial levels of nitric oxide adversely affects microvascular permeability in vitro. To this end we sought to describe the effects of exogenous nitric oxide on the proliferation of intracellular rickettsiae while monitoring the transendothelial electrical resistance as a measure of endothelial barrier integrity. It was determined that the addition of the NO-donor DETA NONOate at certain levels results in a dose-dependent change in electrical resistance across the monolayer while effectively limiting the number of intracellular rickettsiae in human microvascular endothelial cells. The data presented support the idea that nitric oxide produced by infected endothelial cells may be contributing to the changes in vascular permeability that occur during acute rickettsioses. Future experiments aim to elaborate on these results in a model that more clearly depicts the in vivo response as well as to describe the changes that occur with respect to interendothelial junctions.
Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USA.
Michael E
ME
Woods
Gary
G
Wen
Juan P
JP
Olano
D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D002199:Capillary Permeability / Q000502:physiology*; D002460:Cell Line; D002474:Cell-Free System / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D002522:Chlorocebus aethiops; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology*; D018628:Gene Dosage / Q000187:drug effects; D006801:Humans; D008833:Microcirculation / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D020114:Rickettsia conorii / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014709:Vero Cells
D000900:Anti-Bacterial Agents; D009569:Nitric Oxide