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Molecular pathology of pulmonary edema after injury in forensic autopsy cases

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Abstract

The lung is vulnerable to trauma; pulmonary edema starts quickly as part of the systemic responses involved in shock. The present study investigated the molecular pathology of posttraumatic alveolar damage and responses involving pulmonary edema in forensic autopsy cases of injury (n = 66) compared with acute cardiac death cases (n = 13). Intrapulmonary mRNA and immunohistochemical expressions of matrix metalloproteinases (MMPs; MMP-2 and MMP-9), intercellular adhesion molecule-1, claudin-5, and aquaporins (AQPs, AQP-1 and AQP-5) were examined. Subacute injury deaths showed an increase in lung weight similar to that in acute cardiac death, but relative mRNA quantification using the Taqman real-time PCR assay demonstrated different findings among the causes of death; higher expressions were detected for all markers, except for AQP-5 in sharp instrument injury, for MMP-2 in blunt brain injury, and for MMP-9 in non-brain blunt injury, but these expression levels were lower in acute cardiac death. In immunostaining, only MMPs showed differences among the causes of death: MMP-2 expression was evident in most subacute deaths due to blunt brain injury and sharp instrument injury, whereas MMP-9 was intensely positive in those of non-brain blunt injury and sharp instrument injury. These findings suggest significant differences in the mechanism of pulmonary edema among fatal injuries and acute cardiac death, especially between blunt and sharp instrument injury. Systematic analysis of gene expressions using real-time PCR in combination with immunohistochemistry may be useful in evaluating pulmonary damage and responses after injury in death investigations, especially in connection with posttraumatic shock.

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References

  1. Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Isselbacher KJ (2005) Harrison's principles of internal medicine. McGraw-Hill

  2. Woessner JF Jr (1994) The family of matrix metalloproteinases. Ann N Y Acad Sci 732:11–21

    Article  PubMed  CAS  Google Scholar 

  3. Chakrabarti S, Patel KD (2005) Matrix metalloproteinase-2 (MMP-2) and MMP-9 in pulmonary pathology. Exp Lung Res 31(6):599–621

    Article  PubMed  CAS  Google Scholar 

  4. Corbel M, Boichot E, Lagente V (2000) Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung injury. Braz J Med Biol Res 33(7):749–754

    Article  PubMed  CAS  Google Scholar 

  5. van de Stolpe A, van der Saag PT (1996) Intercellular adhesion molecule-1. J Mol Med (Berl) 74(1):13–33

    Article  Google Scholar 

  6. Reutershan J, Ley K (2004) Bench-to-bedside review: acute respiratory distress syndrome—how neutrophils migrate into the lung. Crit Care 8(6):453–461

    Article  PubMed  Google Scholar 

  7. Turksen K, Troy TC (2004) Barriers built on claudins. J Cell Sci 117(Pt 12):2435–2447

    Article  PubMed  CAS  Google Scholar 

  8. Furuse M, Tsukita S (2006) Claudins in occluding junctions of humans and flies. Trends Cell Biol 16(4):181–188

    Article  PubMed  CAS  Google Scholar 

  9. Verkman AS (2002) Aquaporin water channels and endothelial cell function. J Anat 200(6):617–627

    Article  PubMed  CAS  Google Scholar 

  10. Verkman AS, Matthay MA, Song Y (2000) Aquaporin water channels and lung physiology. Am J Physiol Lung Cell Mol Physiol 278(5):L867–879

    PubMed  CAS  Google Scholar 

  11. Benga G (2009) Water channel proteins (later called aquaporins) and relatives: past, present, and future. IUBMB Life 61(2):112–133

    Article  PubMed  CAS  Google Scholar 

  12. Maeda H, Zhu BL, Ishikawa T, Michiue T (2010) Forensic molecular pathology of violent deaths. Forensic Sci Int 203(1–3):83–92

    Article  PubMed  CAS  Google Scholar 

  13. Zhao D, Ishikawa T, Quan L, Li DR, Michiue T, Yoshida C, Komatu A, Chen JH, Zhu BL, Maeda H (2008) Tissue-specific differences in mRNA quantification of glucose transporter 1 and vascular endothelial growth factor with special regard to death investigations of fatal injuries. Forensic Sci Int 177(2–3):176–183

    Article  PubMed  CAS  Google Scholar 

  14. Koppelkamm A, Vennemann B, Fracasso T, Lutz-Bonengel S, Schmidt U, Heinrich M (2010) Validation of adequate endogenous reference genes for the normalisation of qPCR gene expression data in human post mortem tissue. Int J Legal Med 124(5):371–380

    Article  PubMed  Google Scholar 

  15. Miyazato T, Ishikawa T, Michiue T, Maeda H (2012) Molecular pathology of pulmonary surfactants and cytokines in drowning compared with other asphyxiation and fatal hypothermia. Int J Legal Med 126(4):581–587

    Article  PubMed  Google Scholar 

  16. Hayashi T, Ishida Y, Mizunuma S, Kimura A, Kondo T (2009) Differential diagnosis between freshwater drowning and saltwater drowning based on intrapulmonary aquaporin-5 expression. Int J Legal Med 123(1):7–13

    Article  PubMed  Google Scholar 

  17. Ishida K, Zhu BL, Maeda H (2002) A quantitative RT-PCR assay of surfactant-associated protein A1 and A2 mRNA transcripts as a diagnostic tool for acute asphyxial death. Leg Med (Tokyo) 4(1):7–12

    Article  CAS  Google Scholar 

  18. Zhao D, Zhu BL, Ishikawa T, Quan L, Li DR, Maeda H (2006) Real-time RT-PCR quantitative assays and postmortem degradation profiles of erythropoietin, vascular endothelial growth factor and hypoxia-inducible factor 1 alpha mRNA transcripts in forensic autopsy materials. Leg Med (Tokyo) 8(2):132–136

    Article  CAS  Google Scholar 

  19. Chen JH, Michiue T, Ishikawa T, Maeda H (2012) Molecular pathology of natriuretic peptides in the myocardium with special regard to fatal intoxication, hypothermia, and hyperthermia. Int J Legal Med. doi:10.1007/s00414-012-0732-4

  20. Piette MH, Pieters SE, De Letter EA (2011) Evaluation of the agonal stress: can immunohistochemical detection of ubiquitin in the locus coeruleus be useful? Int J Legal Med 125(3):333–340

    Article  PubMed  Google Scholar 

  21. Madea B (2003) Praxis rechtsmedizin: befunderhebung, rekonstruktion, begutachtung. Recherche 67:02

    Google Scholar 

  22. Wang Q, Ishikawa T, Michiue T, Zhu BL, Guan DW, Maeda H (2012) Intrapulmonary aquaporin-5 expression as a possible biomarker for discriminating smothering and choking from sudden cardiac death: a pilot study. Forensic Sci Int 220(1–3):154–157

    Article  PubMed  CAS  Google Scholar 

  23. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408

    Article  PubMed  CAS  Google Scholar 

  24. Maeda H, Ishikawa T, Michiue T (2011) Forensic biochemistry for functional investigation of death: concept and practical application. Leg Med (Tokyo) 13(2):55–67

    Article  CAS  Google Scholar 

  25. Fujita MQ, Zhu BL, Ishida K, Quan L, Oritani S, Maeda H (2002) Serum C-reactive protein levels in postmortem blood—an analysis with special reference to the cause of death and survival time. Forensic Sci Int 130(2–3):160–166

    Article  PubMed  CAS  Google Scholar 

  26. Ishikawa T, Hamel M, Zhu BL, Li DR, Zhao D, Michiue T, Maeda H (2008) Comparative evaluation of postmortem serum concentrations of neopterin and C-reactive protein. Forensic Sci Int 179(2–3):135–143

    Article  PubMed  CAS  Google Scholar 

  27. Quan L, Zhu BL, Ishikawa T, Michiue T, Zhao D, Li DR, Ogawa M, Maeda H (2008) Postmortem serum erythropoietin levels in establishing the cause of death and survival time at medicolegal autopsy. Int J Legal Med 122(6):481–487

    Article  PubMed  CAS  Google Scholar 

  28. Quan L, Zhu BL, Ishikawa T, Michiue T, Zhao D, Ogawa M, Maeda H (2010) Postmortem serum erythropoietin level as a marker of survival time in injury deaths. Forensic Sci Int 200(1–3):117–122

    Article  PubMed  CAS  Google Scholar 

  29. Chen JH, Quan L, Ishikawa T, Michiue T, Wang Q, Zhu BL, Maeda H (2009) Postmortem lung weight with regard to survival time. Leg Med (Tokyo) 11(1):S238–240

    Article  Google Scholar 

  30. Beck-Schimmer B, Schimmer RC, Warner RL, Schmal H, Nordblom G, Flory CM, Lesch ME, Friedl HP, Schrier DJ, Ward PA (1997) Expression of lung vascular and airway ICAM-1 after exposure to bacterial lipopolysaccharide. Am J Respir Cell Mol Biol 17(3):344–352

    PubMed  CAS  Google Scholar 

  31. Calfee CS, Eisner MD, Parsons PE, Thompson BT, Conner ER Jr, Matthay MA, Ware LB (2009) Soluble intercellular adhesion molecule-1 and clinical outcomes in patients with acute lung injury. Intensive Care Med 35(2):248–257

    Article  PubMed  CAS  Google Scholar 

  32. Zhang X, Wu D, Jiang X (2009) ICAM-1 and acute pancreatitis complicated by acute lung injury. JOP 10(1):8–14

    PubMed  Google Scholar 

  33. Jang AS, Concel VJ, Bein K, Brant KA, Liu S, Pope-Varsalona H, Dopico RA Jr, Di YP, Knoell DL, Barchowsky A, Leikauf GD (2011) Endothelial dysfunction and claudin 5 regulation during acrolein-induced lung injury. Am J Respir Cell Mol Biol 44(4):483–490

    Article  PubMed  CAS  Google Scholar 

  34. Soma T, Chiba H, Kato-Mori Y, Wada T, Yamashita T, Kojima T, Sawada N (2004) Thr(207) of claudin-5 is involved in size-selective loosening of the endothelial barrier by cyclic AMP. Exp Cell Res 300(1):202–212

    Article  PubMed  CAS  Google Scholar 

  35. Wu XM, Wang HY, Li GF, Zang B, Chen WM (2009) Dobutamine enhances alveolar fluid clearance in a rat model of acute lung injury. Lung 187(4):225–231

    Article  PubMed  CAS  Google Scholar 

  36. Corry DB, Kiss A, Song LZ, Song L, Xu J, Lee SH, Werb Z, Kheradmand F (2004) Overlapping and independent contributions of MMP2 and MMP9 to lung allergic inflammatory cell egression through decreased CC chemokines. FASEB J 18(9):995–997

    PubMed  CAS  Google Scholar 

  37. Ma WX, Yu TS, Fan YY, Zhang ST, Ren P, Wang SB, Zhao R, Pi JB, Guan DW (2011) Time-dependent expression and distribution of monoacylglycerol lipase during the skin-incised wound healing in mice. Int J Legal Med 125(4):549–558

    Article  PubMed  Google Scholar 

  38. Yu TS, Cheng ZH, Li LQ, Zhao R, Fan YY, Du Y, Ma WX, Guan DW (2010) The cannabinoid receptor type 2 is time-dependently expressed during skeletal muscle wound healing in rats. Int J Legal Med 124(5):397–404

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was in part supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science, and Technology, Japan (grant nos. 21790612 and 22590642).

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Authors and Affiliations

  1. Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, 545-8585, Osaka, Japan

    Qi Wang, Takaki Ishikawa, Tomomi Michiue & Hitoshi Maeda

  2. Medico-legal Consultation and Postmortem Investigation Support Center (MLCPI-SC), Osaka, Japan

    Qi Wang, Takaki Ishikawa, Tomomi Michiue & Hitoshi Maeda

  3. Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, China

    Bao-Li Zhu & Da-Wei Guan

Authors
  1. Qi Wang
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  2. Takaki Ishikawa
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  3. Tomomi Michiue
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  4. Bao-Li Zhu
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  5. Da-Wei Guan
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  6. Hitoshi Maeda
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Correspondence to Qi Wang.

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Wang, Q., Ishikawa, T., Michiue, T. et al. Molecular pathology of pulmonary edema after injury in forensic autopsy cases. Int J Legal Med 126, 875–882 (2012). https://doi.org/10.1007/s00414-012-0758-7

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  • DOI: https://doi.org/10.1007/s00414-012-0758-7

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