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

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.

• Authors: Jeffrey M Dodd-o, Maria L Hristopoulos, Laura E Welsh-Servinsky, Clarke G Tankersley, David B Pearse
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 100 Issue 5 Pg. 1590-5 (May 2006) ISSN: 8750-7587 [Print] United States
• PMID: 16439514 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• Zymosan
• NADPH Oxidases

Topics

• Animals
• Capillary Permeability (physiology)
• Gene Expression Regulation, Enzymologic
• Genetic Predisposition to Disease
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Inbred Strains
• NADPH Oxidases (genetics, physiology)
• Neutrophils (enzymology)
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (genetics, physiopathology)
• Species Specificity
• Time Factors
• Zymosan (pharmacology)