Skip to main content
Log in

Micro-Autoradiographic Assessment of Cell Types Contributing to 2-Deoxy-2-[18F]Fluoro-d-Glucose Uptake During Ventilator-Induced and Endotoxemic Lung Injury

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

The aim of the study was to use micro-autoradiography to investigate the lung cell types responsible for 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake in murine models of acute lung injury (ALI).

Procedures

C57/BL6 mice were studied in three groups: controls, ventilator-induced lung injury (VILI), and endotoxin. VILI was produced by high tidal volumes and zero end-expiratory pressure and endotoxin ALI, by intranasal administration. Following FDG injection, the lungs were processed and exposed to autoradiographic emulsion. Grain density over cells was used to quantify FDG uptake.

Results

Neutrophils, macrophages, and type 2 epithelial cells presented higher grain densities during VILI and endotoxin ALI than controls. Remarkably, cell grain density in specific cell types was dependent on the injury mechanism. Whereas macrophages showed high grain densities during endotoxin ALI, similar to those exhibited by neutrophils, type 2 epithelial cells demonstrated the second highest grain density (with neutrophils as the highest) during VILI.

Conclusions

In murine models of VILI and endotoxin ALI, FDG uptake occurs not only in neutrophils but also in macrophages and type 2 epithelial cells. FDG uptake by individual cell types depends on the mechanism underlying ALI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD (2005) Incidence and outcomes of acute lung injury. N Engl J Med 353:1685–1693

    Article  PubMed  CAS  Google Scholar 

  2. Musch G, Venegas JG, Bellani G, Winkler T, Schroeder T, Petersen B, Harris RS, Melo MF (2007) Regional gas exchange and cellular metabolic activity in ventilator-induced lung injury. Anesthesiology 106:723–735

    Article  PubMed  CAS  Google Scholar 

  3. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS (1999) Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 282:54–61

    Article  PubMed  CAS  Google Scholar 

  4. Suter PM (2006) Lung inflammation in ARDS—friend or foe? N Engl J Med 354:1739–1742

    Article  PubMed  CAS  Google Scholar 

  5. de Prost N, Tucci MR, Vidal Melo MF (2010) Assessment of lung inflammation with 18F-FDG PET during acute lung injury. Am J Roentgenol 195:292–300

    Article  Google Scholar 

  6. Jones HA, Choudhury M, Harris DN (2004) In vivo measurement of circulating leucocyte activation in patients following cardiopulmonary bypass. Nucl Med Biol 31:965–969

    Article  PubMed  Google Scholar 

  7. Chen DL, Schuster DP (2004) Positron emission tomography with [18F]fluorodeoxyglucose to evaluate neutrophil kinetics during acute lung injury. Am J Physiol Lung Cell Mol Physiol 286:L834–40

    Article  PubMed  CAS  Google Scholar 

  8. Costa EL, Musch G, Winkler T, Schroeder T, Harris RS, Jones HA, Venegas JG, Vidal Melo MF (2010) Mild endotoxemia during mechanical ventilation produces spatially heterogeneous pulmonary neutrophilic inflammation in sheep. Anesthesiology 112:658–669

    Article  PubMed  Google Scholar 

  9. Bellani G, Guerra L, Musch G, Zanella A, Patroniti N, Mauri T, Messa C, Pesenti A (2011) Lung regional metabolic activity and gas volume changes induced by tidal ventilation in patients with acute lung injury. Am J Respir Crit Care Med 183:1193–1199

    Article  PubMed  Google Scholar 

  10. de Prost N, Costa EL, Wellman T, Musch G, Winkler T, Tucci MR, Harris RS, Venegas JG, Vidal Melo MF (2011) Effects of surfactant depletion on regional pulmonary metabolic activity during mechanical ventilation. J Appl Physiol 111:1249–1258

    Article  PubMed  Google Scholar 

  11. Rodrigues RS, Miller PR, Bozza FA, Marchiori E, Zimmerman GA, Hoffman JM, Morton KA (2008) FDG-PET in patients at risk for acute respiratory distress syndrome: a preliminary report. Intensive Care Med 34:2273–2278

    Article  PubMed  CAS  Google Scholar 

  12. Chen DL, Bedient TJ, Kozlowski J, Rosenbluth DB, Isakow W, Ferkol TW, Thomas B, Mintun MA, Schuster DP, Walter MJ (2009) [18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation. Am J Respir Crit Care Med 180:533–539

    Article  PubMed  CAS  Google Scholar 

  13. Jones HA, Clark RJ, Rhodes CG, Schofield JB, Krausz T, Haslett C (1994) In vivo measurement of neutrophil activity in experimental lung inflammation. Am J Respir Crit Care Med 149:1635–1639

    PubMed  CAS  Google Scholar 

  14. Jones HA, Sriskandan S, Peters AM, Pride NB, Krausz T, Boobis AR, Haslett C (1997) Dissociation of neutrophil emigration and metabolic activity in lobar pneumonia and bronchiectasis. Eur Respir J 10:795–803

    PubMed  CAS  Google Scholar 

  15. Kubota R, Yamada S, Kubota K, Ishiwata K, Ido T (1993) Micro-autoradiographic method to study [18F]FDG uptake in mouse tissue. Nucl Med Biol 20:183–188

    Article  PubMed  CAS  Google Scholar 

  16. Yamada S, Kubota R, Kubota K, Ishiwata K, Ido T (1990) Localization of [18F]fluorodeoxyglucose in mouse brain neurons with micro-autoradiography. Neurosci Lett 120:191–193

    Article  PubMed  CAS  Google Scholar 

  17. Zhou Z, Kozlowski J, Goodrich AL, Markman N, Chen DL, Schuster DP (2005) Molecular imaging of lung glucose uptake after endotoxin in mice. Am J Physiol Lung Cell Mol Physiol 289:L760–8

    Article  PubMed  CAS  Google Scholar 

  18. Grommes J, Soehnlein O (2011) Contribution of neutrophils to acute lung injury. Mol Med 17:293–307

    Article  PubMed  CAS  Google Scholar 

  19. Mescher A (2009) Junqueira's basic histology. McGraw-Hill Medical, New York

    Google Scholar 

  20. Ochoa CD, Wu S, Stevens T (2010) New developments in lung endothelial heterogeneity: Von Willebrand factor, P-selectin, and the Weibel-Palade body. Semin Thromb Hemost 36:301–308

    Article  PubMed  CAS  Google Scholar 

  21. Massaguer A, Engel P, Perez-del-Pulgar S, Bosch J, Pizcueta P (2000) Production and characterization of monoclonal antibodies against conserved epitopes of P-selectin (CD62P). Tissue Antigens 56:117–128

    Article  PubMed  CAS  Google Scholar 

  22. Hestdal K, Ruscetti FW, Ihle JN, Jacobsen SE, Dubois CM, Kopp WC, Longo DL, Keller JR (1991) Characterization and regulation of RB6-8C5 antigen expression on murine bone marrow cells. J Immunol 147:22–28

    PubMed  CAS  Google Scholar 

  23. Araki M, Hanihara T, Saito T (1988) Histochemical observations on unique rod-like cells in the developing retina of the normal rat. J Neurocytol 17:179–188

    Article  PubMed  CAS  Google Scholar 

  24. Pugin J, Dunn I, Jolliet P, Tassaux D, Magnenat JL, Nicod LP, Chevrolet JC (1998) Activation of human macrophages by mechanical ventilation in vitro. Am J Physiol 275:L1040–50

    PubMed  CAS  Google Scholar 

  25. Vlahakis NE, Schroeder MA, Limper AH, Hubmayr RD (1999) Stretch induces cytokine release by alveolar epithelial cells in vitro. Am J Physiol 277:L167–73

    PubMed  CAS  Google Scholar 

  26. Paik JY, Lee KH, Ko BH, Choe YS, Choi Y, Kim BT (2005) Nitric oxide stimulates 18F-FDG uptake in human endothelial cells through increased hexokinase activity and GLUT1 expression. J Nucl Med 46:365–370

    PubMed  CAS  Google Scholar 

  27. Kerr JS, Reicherter J, Fisher AB (1982) 2-Deoxy-d-glucose uptake by rat granular pneumocytes in primary culture. Am J Physiol 243:C14–9

    PubMed  CAS  Google Scholar 

  28. Chapman KE, Sinclair SE, Zhuang D, Hassid A, Desai LP, Waters CM (2005) Cyclic mechanical strain increases reactive oxygen species production in pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol 289:L834–41

    Article  PubMed  CAS  Google Scholar 

  29. Jafari B, Ouyang B, Li LF, Hales CA, Quinn DA (2004) Intracellular glutathione in stretch-induced cytokine release from alveolar type-2 like cells. Respirology 9:43–53

    Article  PubMed  Google Scholar 

  30. de Prost N, Saumon G (2007) Glucose transport in the lung and its role in liquid movement. Respir Physiol Neurobiol 159:331–337

    Article  PubMed  Google Scholar 

  31. Nolop KB, Maxwell DL, Fleming JS, Braude S, Hughes JM, Royston D (1987) A comparison of 99mTc-DTPA and 113mIn-DTPA aerosol clearances in humans. Effects of smoking, hyperinflation, and in vitro oxidation. Am Rev Respir Dis 136:1112–1116

    Article  PubMed  CAS  Google Scholar 

  32. Ryan JL, Glode LM, Rosenstreich DL (1979) Lack of responsiveness of C3H/HeJ macrophages to lipopolysaccharide: the cellular basis of LPS-stimulated metabolism. J Immunol 122:932–935

    PubMed  CAS  Google Scholar 

  33. Ryan JL, Yohe WB (1981) Lymphocyte mediation of lipopolysaccharide-stimulated macrophage metabolism. J Immunol 127:912–916

    PubMed  CAS  Google Scholar 

  34. Chen DL, Rosenbluth DB, Mintun MA, Schuster DP (2006) FDG-PET imaging of pulmonary inflammation in healthy volunteers after airway instillation of endotoxin. J Appl Physiol 100:1602–1609

    Article  PubMed  CAS  Google Scholar 

  35. Gando S, Kameue T, Matsuda N, Sawamura A, Hayakawa M, Kato H (2004) Systemic inflammation and disseminated intravascular coagulation in early stage of ALI and ARDS: role of neutrophil and endothelial activation. Inflammation 28:237–244

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partially supported by the National Heart, Lung, and Blood Institute/National Institutes of Health grant HL 5R01HL086827. We would like to express our profound gratitude to Dr. Rosemary Jones and Diane E. Capen for the guidance and criticism on the experiments and manuscript. We would also like to thank Dr. Mauro Tucci for performance of pilot studies, Steve Weise for the technical aspects in manipulation of FDG samples, and Teri Bowman for assistance with methodology for immunohistochemistry.

Conflict of Interest

None of the authors has any conflict of interest associated with this project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marcos F. Vidal Melo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saha, D., Takahashi, K., de Prost, N. et al. Micro-Autoradiographic Assessment of Cell Types Contributing to 2-Deoxy-2-[18F]Fluoro-d-Glucose Uptake During Ventilator-Induced and Endotoxemic Lung Injury. Mol Imaging Biol 15, 19–27 (2013). https://doi.org/10.1007/s11307-012-0575-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-012-0575-x

Key Words

Navigation