Deletion of the gene encoding calcitonin and calcitonin gene-related peptide a does not affect the outcome of severe infection in mice

Michael J. Tuvim, Cecilia G. Clement, Eileen Su Chen Huang, Gilbert J. Cote, Scott E. Evans, Xiudong Lei, Leonard J. Deftos, Robert F. Gagel, Burton F. Dickey

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Procalcitonin (PCT) is expressed in nonthryoidal tissues of humans during severe infections. Serum PCT levels are measured to diagnose and guide therapy, and there is some evidence that PCT may also contribute to the pathogenesis of sepsis. We tested whether disruption of the gene encoding PCT in mice affected the course of sepsis. Mice with exons 2-5 of the gene encoding calcitonin/calcitonin gene-related polypeptide a (Calca) knocked out and congenic C57BL/6J control mice were challenged with aerosolized Streptococcus pneumoniae or Pseudomonas aeruginosa, or injected intraperitoneally with S. pneumoniae. There were no significant differences in the survival of knockout and control mice in the two pneumonia models, and no significant differences in weight loss, splenic bacterial counts, or blood leukocyte levels in the peritoneal sepsis model. To verify disruption of the Calca gene in knockout mice, the absence of calcitonin in the serum of knockout mice and its presence and inducibility in control mice were confirmed. To evaluate PCT expression innonthyroidal tissuesofcontrolmice, transcriptsweremeasured inmultiple organs. PCT transcriptswere not significantly expressed in liver or spleen of control mice challenged with aerosolized P. aeruginosa or intraperitoneal endotoxin, andwere expressed in lung only at lowlevels, even though serumIL-6 rose 3,548-fold.We conclude that mice are not an ideal loss-of-functionmodel to test the role of PCT in the pathogenesis of sepsis because of lownonendocrine PCT expression during infection and inflammation. Nonetheless, our studies demonstrate that nonendocrine PCT expression is not necessary for adverse outcomes from sepsis.

Original languageEnglish (US)
Pages (from-to)151-155
Number of pages5
JournalAmerican journal of respiratory cell and molecular biology
Volume49
Issue number1
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • Calcitonin
  • Pneumonia
  • Procalcitonin
  • Sepsis

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Deletion of the gene encoding calcitonin and calcitonin gene-related peptide a does not affect the outcome of severe infection in mice'. Together they form a unique fingerprint.

  • Cite this