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
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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