Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice

Paul H. Dahm, Jeremy B. Richards, Harry Karmouty-Quintana, Kevin R. Cromar, Sanjiv Sur, Roger E. Price, Farhan Malik, Chantal Y. Spencer, Ramon X. Barreno, Syed S. Hashmi, Michael R. Blackburn, Ikram U. Haque, Richard A. Johnston

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin (ob/ob mice) or the long isoform of the leptin receptor (db/db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure (Cpefat mice). Accordingly, Cpefat and lean, wild-type (C57BL/6) mice were sensitized to OVA and then challenged with either aerosolized PBS or OVA. Compared with genotype-matched, OVA-sensitized and PBS-challenged mice, OVA sensitization and challenge elicited airway obstruction and increased BALF eosino-phils, macrophages, neutrophils, IL-4, IL-13, IL-18, and chemerin. However, OVA challenge enhanced airway obstruction and pulmonary inflammation in Cpefat compared with wild-type mice. These results demonstrate that OVA sensitization and challenge enhance airway obstruction in obese mice regardless of the genetic basis of obesity, whereas the degree of OVA-induced pulmonary inflammation is dependent on the genetic modality of obesity induction. These results have important implications for animal models of asthma, as modeling the pulmonary phenotypes for subpopulations of atopic, obese asthmatics critically depends on selecting the appropriate mouse model.

Original languageEnglish (US)
Pages (from-to)R621-R633
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume307
Issue number6
DOIs
StatePublished - Sep 15 2014

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Carboxypeptidase H
Mechanics
Airway Obstruction
Pneumonia
Antigens
Obese Mice
Obesity
Bronchoalveolar Lavage Fluid
Leptin Receptors
Interleukin-18
Interleukin-13
Ovalbumin
Leptin
Inbred C57BL Mouse
Eosinophils
Interleukin-4
Energy Metabolism
Protein Isoforms
Neutrophils
Asthma

Keywords

  • Asthma
  • Atopic
  • Eosinophil
  • Interleukin-13
  • Ovalbumin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Medicine(all)

Cite this

Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice. / Dahm, Paul H.; Richards, Jeremy B.; Karmouty-Quintana, Harry; Cromar, Kevin R.; Sur, Sanjiv; Price, Roger E.; Malik, Farhan; Spencer, Chantal Y.; Barreno, Ramon X.; Hashmi, Syed S.; Blackburn, Michael R.; Haque, Ikram U.; Johnston, Richard A.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 307, No. 6, 15.09.2014, p. R621-R633.

Research output: Contribution to journalArticle

Dahm, PH, Richards, JB, Karmouty-Quintana, H, Cromar, KR, Sur, S, Price, RE, Malik, F, Spencer, CY, Barreno, RX, Hashmi, SS, Blackburn, MR, Haque, IU & Johnston, RA 2014, 'Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice', American Journal of Physiology - Regulatory Integrative and Comparative Physiology, vol. 307, no. 6, pp. R621-R633. https://doi.org/10.1152/ajpregu.00205.2014
Dahm, Paul H. ; Richards, Jeremy B. ; Karmouty-Quintana, Harry ; Cromar, Kevin R. ; Sur, Sanjiv ; Price, Roger E. ; Malik, Farhan ; Spencer, Chantal Y. ; Barreno, Ramon X. ; Hashmi, Syed S. ; Blackburn, Michael R. ; Haque, Ikram U. ; Johnston, Richard A. / Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2014 ; Vol. 307, No. 6. pp. R621-R633.
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