Recombinant human tissue non-specific alkaline phosphatase successfully counteracts lipopolysaccharide induced sepsis in mice

B. Bender, M. Baranyi, A. Kerekes, L. Bodrogi, R. Brands, P. Uhrin, Z. Bösze

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Sepsis is a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Sepsis can lead to shock, multiple organ failure and death especially if not recognized early and treated promptly. Molecular mechanisms underlying the systemic inflammatory response syndrome associated with sepsis are still not completely defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. In this study we investigated a possibility of combating sepsis in a mouse model by intravenous treatment with recombinant human tissue nonspecific alkaline phosphatase (rhTNAP) derived from transgenic rabbit milk. We induced sepsis in mice by intraperitoneal injection of LPS and three hours later treated experimental group of mice by intravenous injection with rhTNAP derived from transgenic rabbits. Such treatment was proved to be physiologically effective in this model, as administration of recombinant rhTNAP successfully combated the decrease in body temperature and resulted in increased survival of mice (80 % vs. 30 % in a control group). In a control experiment, also the administration of bovine intestinal alkaline phosphatase by intravenous injection proved to be effective in increasing survival of mice treated with LPS. Altogether, present work demonstrates the redeeming effect of the recombinant tissue non-specific AP derived from milk of genetically modified rabbits in combating sepsis induced by LPS.

Original languageEnglish
Pages (from-to)731-738
Number of pages8
JournalPhysiological Research
Volume64
Issue number5
Publication statusPublished - 2015

Fingerprint

Lipopolysaccharides
Sepsis
Alkaline Phosphatase
Rabbits
Intravenous Injections
Milk
Systemic Inflammatory Response Syndrome
Multiple Organ Failure
Intraperitoneal Injections
Body Temperature
human ALPL protein
Shock
Therapeutics
Control Groups
Infection

Keywords

  • Lipopolysaccharides
  • Mice
  • Sepsis
  • Survival
  • Tissue non-specific alkaline phosphatase

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology

Cite this

Recombinant human tissue non-specific alkaline phosphatase successfully counteracts lipopolysaccharide induced sepsis in mice. / Bender, B.; Baranyi, M.; Kerekes, A.; Bodrogi, L.; Brands, R.; Uhrin, P.; Bösze, Z.

In: Physiological Research, Vol. 64, No. 5, 2015, p. 731-738.

Research output: Contribution to journalArticle

Bender, B, Baranyi, M, Kerekes, A, Bodrogi, L, Brands, R, Uhrin, P & Bösze, Z 2015, 'Recombinant human tissue non-specific alkaline phosphatase successfully counteracts lipopolysaccharide induced sepsis in mice', Physiological Research, vol. 64, no. 5, pp. 731-738.
Bender, B. ; Baranyi, M. ; Kerekes, A. ; Bodrogi, L. ; Brands, R. ; Uhrin, P. ; Bösze, Z. / Recombinant human tissue non-specific alkaline phosphatase successfully counteracts lipopolysaccharide induced sepsis in mice. In: Physiological Research. 2015 ; Vol. 64, No. 5. pp. 731-738.
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