PIP, Not FiO₂ Regulates Expression of MMP-9 in the Newborn Rabbit VILI with Different Mechanical Ventilation Strategies

Shaodong Hua, Xiaoying Zhang, Shengli An, Xiuxiang Liu, Zhichun Feng

Department of Biostatistics, South Medical University, Guangzhou, China.
Department of Pediatrics, BaYi Children’s Hospital of the General Military Hospital of Beijing PLA, Beijing, China.
The Hospital Affilicated Binzhou Medicall University, Binzhou, China.

DOI: 10.4236/cm.2013.44017                

Abstract

Background: Results from experimental and clinical studies have shown that mechanical ventilation or/and hyperoxia may aggravate a pre-existing lung injury or even cause lung injury in healthy lungs by affecting the expression of MMP-9, but the MMP-9 effects are controversial. How are MMP-9 regulated when multicausative factors of injury such as different FiO₂, PIP, and respiratory time (RT) impose simultaneously on lungs? Methods: Newborn New Zealand white rabbits were randomly allocated to an unventilated air control group or to one of the 2 × 3 × 3 ventilation strategies by using a factorial design, with different FiO₂, PIP, and RT. Then, lung wet-to-dry ratio (W/D), lung histopathology scores, transmission electron microscope, and cells in BALF were analyzed in these different groups. MMP-9 levels were studied by immunohistochemistry and ELISA. Results: MMP-9 levels were significantly different among 3 PIP ventilation regimes (F = 7.215) and MPIP group was the highest among 3 PIP groups. The lung histopathology score in 100% oxygen was significantly higher than in 45% oxygen group (F = 9.037) and MPIP group was the lowest among 3 PIP groups (F = 57.515) and RT 6 h was more serious than RT 1 h. MMP-9 positively correlated with monocytes, but negatively correlated with neutrophils and lung injury histopathology scores. Conclusions: Different PIP and FiO₂ exert simultaneously on newborn lung in newborn rabbits ventilation, only mechanical stretch stimulation affects MMP-9 synthesis. Advisable mechanical stretch can promote MMP-9 expression and has protective role in lung in VILI. HPIP causes barotraumas and LPIP induces atelectrauma.

Keywords

Mechanical Ventilation; Lung Injury; Matrix Metalloproteinase; Newborn Rabbit; Fraction of Inspired Oxygen; Peak Inspiratory Pressure

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	P. L. Davies, O. B. Spiller, M. L. Beeton, et al., “Relationship of Proteinases and Proteinase Inhibitors with Microbial Presence in Chronic Lung Disease of Prematurity,” Thorax, Vol. 65, No. 3, 2010, pp. 246-251. http://dx.doi.org/10.1136/thx.2009.116061
[2]	H. D. Foda, E. E. Rollo, M. Drews, et al., “VentilatorInduced Lung Injury Upregulates and Activates Gelatinases and EMMPRIN: Attenuation by the Synthetic Matrix Metalloproteinase Inhibitor, Prinomastat (AG3340),” American Journal of Respiratory Cell and Molecular Biology, Vol. 25, No. 6, 2001, pp. 717-724. http://dx.doi.org/10.1165/ajrcmb.25.6.4558f
[3]	J. H. Kim, M. H. Suk, D. W. Yoon, et al., “Inhibition of Matrix Metalloproteinase-9 Prevents Neutrophilic Inflammation in Ventilator-Induced Lung Injury,” American Journal of Physiology Lung Cellular and Molecular, Vol. 291, No. 4, 2006, pp. L580-L587. http://dx.doi.org/10.1152/ajplung.00270.2005
[4]	S. Buckley, B. Driscoll, W. Shi, et al., “Migration and Gelatinases in Cultured Fetal, Adult, and Hyperoxic Alveolar Epithelial Cells,” American Journal of Physiology Lung Cellular and Molecular, Vol. 281, No. 2, 2001, pp. L427-L434.
[5]	C. Delclaux, M. P. d’Ortho, C. Delacourt, et al., “Gelatinases in Epithelial Lining Fluid of Patients with Adult Respiratory Distress Syndrome,” American Journal of Physiology, Vol. 272, No. 3, 1997, pp. L442-L451.
[6]	B. Ricou, L. Nicod, S. Lacraz, et al., “Matrix Metalloproteinases and TIMP in Acute Respiratory Distress Syndrome,” American Journal of Respiratory and Critical Care Medicine, Vol. 154, No. 2, 1996, pp. 346-352. http://dx.doi.org/10.1164/ajrccm.154.2.8756805
[7]	H. K. Yoon, H. Y. Cho and S. R. Kleeberger, “Protective Role of Matrix Metalloproteinase-9 in Ozone-Induced Airway Inflammation,” Environmental Health Perspectives, Vol. 115, No. 11, 2007, pp. 1557-1563. http://dx.doi.org/10.1289/ehp.10289
[8]	H. Lukkarinen, A. Hogmalm, U. Lappalainen, et al., “Matrix Metalloproteinase-9 Deficiency Worsens Lung Injury in a Model of Bronchopulmonary Dysplasia,” American Journal of Respiratory Cell and Molecular Biology, Vol. 41, No. 1, 2009, pp. 59-68. http://dx.doi.org/10.1165/rcmb.2008-0179OC
[9]	G. M. Albaiceta, A. Gutierrez-Fernandez, D. Parra, et al., “Lack of Matrix Metalloproteinasec9 Worsens Ventilator-Induced Lung Injury,” American Journal of Physiology Lung Cellular and Molecular, Vol. 294, No. 3, 2008, pp. L535-L543. http://dx.doi.org/10.1152/ajplung.00334.2007
[10]	V. Lagente, B. Manoury, S. Nenan, et al., “Role of Matrix Metalloproteinase in the Development of Airway Inflammation and Remodeling,” Brazilian Journal of Medical and Biological Research, Vol. 38, No. 10, 2005, pp. 1521-1530. http://dx.doi.org/10.1590/S0100-879X2005001000009
[11]	E. K. Wolthuis, A. P. Vlaar, G. Choi, et al., “Mechanical Ventilation Using Non-Injurious Ventilation Settings Causes Lung Injury in the Absence of Pre-Existing Lung Injury in Healthy Mice,” Critical Care, Vol. 13, No. 1, 2009, p. R1. http://dx.doi.org/10.1186/cc7688
[12]	E. K. Wolthuis, A. P. Vlaar, G. Choi, et al., “Recombinant Human Soluble Tumor Necrosis Factor-Alpha Receptor Fusion Protein Partly Attenuates Ventilator-Induced Lung Injury,” Shock, Vol. 31, No. 3, 2009, pp. 262-266. http://dx.doi.org/10.1097/SHK.0b013e31817d42dd
[13]	P. Svedin, H. Hagberg, K. Savman, et al., “Matrix Metalloproteinase-9 Gene Knock-out Protects the Immature Brain after Cerebral Hypoxia-Ischemia,” The Journal of Neuroscience, Vol. 27, No. 7, 2007, pp. 1511-1518. http://dx.doi.org/10.1523/JNEUROSCI.4391-06.2007
[14]	D. Dreyfuss and G. Saumon, “Ventilator-Induced Lung Injury: Lessons from Experimental Studies,” American Journal of Respiratory and Critical Care Medicine, Vol. 157, No. 1, 1998, pp. 294-323. http://dx.doi.org/10.1164/ajrccm.157.1.9604014
[15]	D. Dreyfuss, P. Soler, G. Basset, et al., “High Inflation Pressure Pulmonary Edema: Respective Effects of High Pressure, High Tidal Volume and Positive End-Expiratory Pressure,” American Review of Respiratory Disease, Vol. 137, No. 5, 1988, pp. 1159-1164.
[16]	P. M. Yao, J. M. Buhler, M. P. d’Ortho, et al., “C. Expression of Matrix Metalloproteinase Gelatinases A and B by Cultured Epithelial Cells from Human Bronchial Explants,” The Journal of Biological Chemistry, Vol. 271, No. 26, 1996, pp. 15580-15589. http://dx.doi.org/10.1074/jbc.271.26.15580
[17]	A. Pardo, K. Ridge, B. Uhal, et al., “Lung Alveolar Epithelial Cells Synthesize Interstitial Collagenase and Gelatinases A and B in Vitro,” The International Journal of Biochemistry & Cell Biology, Vol. 29, No. 6, 1997, pp. 901-910. http://dx.doi.org/10.1016/S1357-2725(97)00030-7
[18]	H. G. Welgus, E. J. Campbell, J. D. Cury, et al., “Neutral Metalloproteinases Produced by Human Mononuclear Phagocytes. Enzyme Profile, Regulation, and Expression during Cellular Development,” Journal of Clinical Investigation, Vol. 86, No. 5, 1990, pp. 1496-1502. http://dx.doi.org/10.1172/JCI114867
[19]	Y. Gushima, K. Ichikado, M. Suga, et al., “Expression of Matrix Metalloproteinases in Pigs with Hyperoxia-Induced Acute Lung Injury,” European Respiratory Journal, Vol. 18, No. 5, 2001, pp. 827-837. http://dx.doi.org/10.1183/09031936.01.00049201
[20]	J. Pugin, I. Dunn, P. Jolliet, et al. “Activation of Human Macrophages by Mechanical Ventilation in Vitro,” American Journal of Physiology, Vol. 275, No. 6, 1998, pp. L1040-L1050.
[21]	D. F. Gibbs, R. L. Warner, S. J. Weiss, et al., “Characterization of Matrixmetallop Roteinases Produced by Rat Alveolar Macrophages,” American Journal of Respiratory Cell and Molecular Biology, Vol. 20, No. 6, 1999, pp. 1136-1144. http://dx.doi.org/10.1165/ajrcmb.20.6.3483
[22]	R. Renckens, J. J. Roelofs, S. Florquin, et al., “Matrix Metalloproteinase-9 Deficiency Impairs Host Defense against Abdominal Sepsis,” The Journal of Immunology, Vol. 176, No. 6, 2006, pp. 3735-3741.
[23]	K. Bry, A. Hogmalm and E. Backstrom, “Mechanisms of Inflammatory Lung Injury in the Neonate: Lessons from a Transgenic Mouse Model of Bronchopulmonary Dysplasia,” Seminars in Perinatology, Vol. 34, No. 3, 2010, pp. 211-221. http://dx.doi.org/10.1053/j.semperi.2010.02.006
[24]	S. Cabrera, M. Gaxiola, J. L. Arreola, et al., “Overexpression of MMP9 in Macrophages Attenuates Pulmonary Fibrosis Induced by Bleomycin,” The International Journal of Biochemistry & Cell Biology, Vol. 39, No. 12, 2007, pp. 2324-2338. http://dx.doi.org/10.1016/j.biocel.2007.06.022
[25]	A. Ito, A. Mukaiyama, Y. Itoh, et al., “Degradation of Interleukin 1beta by Matrix Metalloproteinases,” The Journal of Biological Chemistry, Vol. 271, No. 25, 1996, pp. 14657-14660. http://dx.doi.org/10.1074/jbc.271.25.14657
[26]	W. C. Parks and R. P. Mecham, “Gelatinase B: Structure, Regulation, and Function,” In: Matrix Metalloproteinases, Academic Press, San Diego, 1998, pp. 115-148.
[27]	C. A. Owen, Z. Hu, B. Barrick, et al., “Inducible Expression of Tissue Inhibitor of Metalloproteinases-Resistant Matrix Metalloproteinase-9 on the Cell Surface of Neutrophils,” American Journal of Respiratory Cell and Molecular Biology, Vol. 29, No. 3, 2003, pp. 283-294. http://dx.doi.org/10.1165/rcmb.2003-0034OC
[28]	A. S. Slutsky, “Ventilator-Induced Lung Injury: From Barotrauma to Biotrauma,” Respiratory Care, Vol. 50, No. 5, 2005, pp. 646-659.
[29]	C. C. dos Santos and A. S. Slutsky, “The Contribution of Biophysical Lung Injury to the Development of Biotrauma,” Annual Review of Physiology, Vol. 68, 2006, pp. 585-618. http://dx.doi.org/10.1146/annurev.physiol.68.072304.113443
[30]	L. Gattinoni, E. Carlesso, P. Cadringher, et al., “Physical and Biological Triggers of Ventilator-Induced Lung Injury and Its Prevention,” European Respiratory Journal, Vol. 47, 2003, pp. 15s-25s. http://dx.doi.org/10.1183/09031936.03.00021303
[31]	F. Kheradmand, E. Werner, P. Tremble, et al., “Role of Rac1 and Oxygen Radicals in Collagenase-1 Expression Induced by Cell Shape Change,” Science, Vol. 280, No. 5365, 1998, pp. 898-902. http://dx.doi.org/10.1126/science.280.5365.898
[32]	R. L. Hawwa, M. A. Hokenson, Y. Wang, et al., “Differential Expression of MMP-2 and -9 and Their Inhibitors in Fetal Lung Cells Exposed to Mechanical Stretch: Regulation by IL-10,” Lung, Vol. 189, No. 4, 2011, pp. 341-349. http://dx.doi.org/10.1007/s00408-011-9310-7
[33]	G. Opdenakker, P. E. Van den Steen, J. Van Damme, “Gelatinase B: A Tuner and Amplifier of Immune Functions,” Trends in Immunology, Vol. 22, No. 10, 2001, pp. 571-579. http://dx.doi.org/10.1016/S1471-4906(01)02023-3
[34]	J. J. Atkinson and R. M. Senior, “Matrix Metalloproteinase-9 in Lung Remodeling,” American Journal of Respiratory Cell and Molecular Biology, Vol. 28, No. 1, 2003, pp. 12-24. http://dx.doi.org/10.1165/rcmb.2002-0166TR
[35]	S. Chakrabarti and K. D. Patel, “Matrix Metalloproteinase-2 (MMP-2) and MMP-9 in Pulmonary Pathology,” Experimental Lung Research, Vol. 31, No. 6, 2005, pp. 599-621. http://dx.doi.org/10.1080/019021490944232