Regulation of the acute phase response genes alpha1-acid glycoprotein and alpha1-antitrypsin correlates with sensitivity to thermal injury

D. A. Gilpin, C. C. Hsieh, D. T. Kuninger, David Herndon, John Papaconstantinou

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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 (α1-acid glycoprotein and α1-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 α1- glycoprotein, rat albumin, and mouse α1-antitrypsin cDNAs. Relative amounts of α1-glycoprotein, α1-antitrypsin, and albumin mRNAs were determined by means of densitometric analyses. Results. All three strains elicit both a positive and negative acute (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.

Original languageEnglish (US)
Pages (from-to)664-673
Number of pages10
JournalSurgery
Volume119
Issue number6
DOIs
StatePublished - 1996

Fingerprint

Acute-Phase Reaction
Glycoproteins
Hot Temperature
Acids
Wounds and Injuries
Genes
Acute-Phase Proteins
Albumins
Aptitude
Buffaloes
Body Surface Area
Liver
Inbred F344 Rats
Northern Blotting
Sprague Dawley Rats
Complementary DNA
Communication
RNA
Weights and Measures
Messenger RNA

ASJC Scopus subject areas

  • Surgery

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Regulation of the acute phase response genes alpha1-acid glycoprotein and alpha1-antitrypsin correlates with sensitivity to thermal injury. / Gilpin, D. A.; Hsieh, C. C.; Kuninger, D. T.; Herndon, David; Papaconstantinou, John.

In: Surgery, Vol. 119, No. 6, 1996, p. 664-673.

Research output: Contribution to journalArticle

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abstract = "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 (α1-acid glycoprotein and α1-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 α1- glycoprotein, rat albumin, and mouse α1-antitrypsin cDNAs. Relative amounts of α1-glycoprotein, α1-antitrypsin, and albumin mRNAs were determined by means of densitometric analyses. Results. All three strains elicit both a positive and negative acute (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.",
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