Regulation of the acute phase response genes alpha 1-acid glycoprotein and alpha 1-antitrypsin correlates with sensitivity to thermal injury.

BACKGROUND

The response to thermal injury is a complex physiologic process requiring communication between sites of injury and distal target organs. The liver, one of these target organs, synthesizes a family of secretory proteins, the acute phase reactants (APRs), that carries out specific protective functions. This study investigates the response of positively regulated (alpha 1-acid glycoprotein and alpha 1-antitrypsin) and negatively regulated (albumin) APR genes to severe thermal injury in three rat strains with differing abilities to survive thermal stress.

METHODS

Age and weight matched male Buffalo, Sprague-Dawley, and Fischer 344, 12- to 16-week-old rats (275 to 325 gm) received a 40% total body surface area scald burn. Total RNA was isolated from livers at 0, 2, 5, 12, 24, and 48 hours. Northern blot hybridization was performed with 32P-labeled rat alpha 1-glycoprotein, rat albumin, and mouse alpha 1-antitrypsin cDNAs. Relative amounts of alpha 1-glycoprotein, alpha 1-antitrypsin, and albumin mRNAs were determined by means of densitometric analyses.

RESULTS

All three strains elicit both a positive and negative acute phase (AP) response. Significant differences were observed in the degree and kinetics between strains. Those more sensitive to thermal injury exhibited a more intense positive AP response and possibly a delayed recovery. The AP response between these strains correlates with the variation in ability to survive severe trauma.

CONCLUSIONS

The differences in the kinetics and intensity of induction of APR genes between Buffalo, Sprague-Dawley, and Fischer rat strains suggest that the least intense AP response and its timely recovery correlated with the ability to survive a severe thermal injury and that, conversely, the more intense and prolonged response correlated with sensitivity to severe thermal injury. We propose that this may be a basis for variation in survival to thermal injury.