Rapid Vascular Responses to Anthrax Lethal Toxin in Mice Containing a Segment of Chromosome 11 from the CAST/Ei Strain on a C57BL/6 Genetic Background
Autor: | Jeffrey D. Radel, Laura E. Kelly, Edward J. Doyle, Cassandra L. Buchheit, Ryan J. Gallagher, John G. Wood, Kelsey J. Weigel, Kenneth A. Bradley, Laura Rues, Steven M. LeVine |
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Rok vydání: | 2012 |
Předmět: |
Bacterial Diseases
C57BL/6 Anatomy and Physiology Interleukin-1beta lcsh:Medicine Vascular permeability Cardiovascular System Monocytes Mice 0302 clinical medicine Genetics of the Immune System Mesentery lcsh:Science Lung Immune Response 0303 health sciences Multidisciplinary biology Interleukin-18 Inflammasome Innate Immunity Bacillus anthracis Infectious Diseases medicine.anatomical_structure Circulatory Physiology Systemic administration Medicine Antibody Intravital microscopy Research Article medicine.drug Immune Cells Bacterial Toxins Immunology Mice Transgenic Anthrax Capillary Permeability 03 medical and health sciences Genetics medicine Animals Genetic Predisposition to Disease Biology Immunity to Infections 030304 developmental biology Inflammation Antigens Bacterial lcsh:R Immunity biology.organism_classification Chromosomes Mammalian Molecular biology Small intestine Mice Inbred C57BL Disease Models Animal Regional Blood Flow biology.protein Blood Vessels lcsh:Q Animal Genetics 030215 immunology |
Zdroj: | PLoS ONE, Vol 7, Iss 7, p e40126 (2012) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Host allelic variation controls the response to B. anthracis and the disease course of anthrax. Mouse strains with macrophages that are responsive to anthrax lethal toxin (LT) show resistance to infection while mouse strains with LT non-responsive macrophages succumb more readily. B6.CAST.11M mice have a region of chromosome 11 from the CAST/Ei strain (a LT responsive strain) introgressed onto a LT non-responsive C57BL/6J genetic background. Previously, B6.CAST.11M mice were found to exhibit a rapid inflammatory reaction to LT termed the early response phenotype (ERP), and displayed greater resistance to B. anthracis infection compared to C57BL/6J mice. Several ERP features (e.g., bloat, hypothermia, labored breathing, dilated pinnae vessels) suggested vascular involvement. To test this, Evan’s blue was used to assess vessel leakage and intravital microscopy was used to monitor microvascular blood flow. Increased vascular leakage was observed in lungs of B6.CAST.11M mice compared to C57BL/6J mice 1 hour after systemic administration of LT. Capillary blood flow was reduced in the small intestine mesentery without concomitant leukocyte emigration following systemic or topical application of LT, the latter suggesting a localized tissue mechanism in this response. Since LT activates the Nlrp1b inflammasome in B6.CAST.11M mice, the roles of inflammasome products, IL-1β and IL-18, were examined. Topical application to the mesentery of IL-1β but not IL-18 revealed pronounced slowing of blood flow in B6.CAST.11M mice that was not present in C57BL/6J mice. A neutralizing anti-IL-1β antibody suppressed the slowing of blood flow induced by LT, indicating a role for IL-1β in the response. Besides allelic differences controlling Nlrp1b inflammasome activation by LT observed previously, evidence presented here suggests that an additional genetic determinant(s) could regulate the vascular response to IL-1β. These results demonstrate that vessel leakage and alterations to blood flow are part of the rapid response in mice resistant to B. anthracis infection. |
Databáze: | OpenAIRE |
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