Strain-specific differences in sensitivity to ischemia-reperfusion lung injury in mice

Jeffrey M Dodd-o, Maria L. Hristopoulos, Laura E. Welsh-Servinsky, Clarke G. Tankersley, David B Pearse

Research output: Contribution to journalArticle

Abstract

Ischemia-reperfusion (I/R) lung injury is characterized by increased pulmonary endothelial permeability and edema, but the genetic basis for this injury is unknown. We utilized an in vivo mouse preparation of unilateral lung I/R to evaluate the genetic determinants of I/R lung injury. An index of pulmonary vascular protein permeability was measured by the ratio of left-to-right lung Evans blue dye of eight inbred mouse strains after 30 min of left lung ischemia and 150 min of reperfusion. The order of strain-specific sensitivity to I/R lung injury was BALB/c > SJL/J > CBA/J > C57BL/6J > 129/J > A/J > C3H/H3J > SWR/J. The reciprocal F1 offspring of the BALB/c and SWR/J progenitor strains had intermediate phenotypes but a differing variance. A similar pattern of right lung Evans blue dye content suggested the presence of contralateral injury because baseline vascular permeability was not different. Lung I/R injury was attenuated by NADPH oxidase inhibition, indicating a role for NADPH oxidase-derived reactive oxygen species (ROS). There was no strain-dependent difference in lung NADPH oxidase expression. Strain-related differences in zymosan-stimulated neutrophil ROS production did not correlate with I/R lung injury in that neutrophil ROS production in SWR/J mice was greater than C57BL/6J but not different from BALB/c mice. These data indicate the presence of a genetic sensitivity to lung I/R injury that involves multiple genes including a maternal-related factor. Although neutrophil-derived ROS production is also modulated by genetic factors, the pattern did not explain the genetic sensitivity to lung I/R injury.

Original languageEnglish (US)
Pages (from-to)1590-1595
Number of pages6
JournalJournal of Applied Physiology
Volume100
Issue number5
DOIs
Publication statusPublished - May 2006

    Fingerprint

Keywords

  • Edema
  • Evans blue dye
  • NADPH oxidase
  • p22
  • Vascular permeability

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this