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Vol. 43. Issue 10.
Pages 542-548 (January 2007)
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Vol. 43. Issue 10.
Pages 542-548 (January 2007)
Original Articles
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Interleukin-8 Expression in Lung Tissue During Ischemia-Reperfusion
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José María Matillaa,
Corresponding author
jmmatilla17@hotmail.com

Correspondence: Dr. J.M. Matilla González. Servicio de Cirugía Torácica. Hospital Clínico Universitario de Valladolid. Ramón y Cajal, 3. 47005 Valladolid. España
, Mariano García-Yustea, Mariano Sánchez Crespob, Manuel J. Gayoso, Félix Herasa, Marta Jiménez Pradaa, Andrés Alonsob, Guillermo Ramosa
a Unidad de Cirugía Torácica Experimental, Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain
b Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid-CSIC, Valladolid, Spain
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Objective

Local cytokine production is a pathogenic factor in ischemia-reperfusion injury in early graft dysfunction. This study analyzed interleukin 8 (IL-8) messenger RNA (mRNA) expression in lung tissue and the association between IL-8 mRNA levels and interstitial lung changes in an experimental model of warm lung ischemia-reperfusion.

MATERIAL AND METHODS

We studied 16 New Zealand rabbits divided into 3 groups: control, ischemia (tissue taken from right lower lobe after 1, 2, or 3 hours of ischemia), and reperfusion (tissue taken from right upper and middle lobes after 1 hour of ischemia and 1, 2, or 3 hours of reperfusion). Expression of IL-8 mRNA was determined by reverse transcription and polymerase chain reaction. Interstitial infiltration by polymorphonuclear neutrophils was determined. The Mann-Whitney U-test was used for statistical comparisons, with P<.05 considered to indicate a significant result.

RESULTS

During ischemia, IL-8 mRNA levels were elevated at the end of hour 1 (P=.009) with respect to the control group, but not thereafter. Interstitial changes were minimal. IL-8 mRNA levels during reperfusion were similar to those observed during ischemia, with a slight increase at the end of hour 2. There were no significant differences between hours 1, 2, and 3. Polymorphonuclear neutrophil recruitment occurred at the beginning of reperfusion (P=.014), but no significant differences were observed at hours 2 or 3. Progressive thickening of alveolar septa and edema was documented.

CONCLUSIONS

Changes in IL-8 mRNA expression during ischemia precede interstitial infiltration by polymorphonuclear neutrophils during reperfusion, suggesting that the 2 processes are related. Quantification of IL-8 mRNA expression could facilitate early diagnosis of graft dysfunction.

Key words:
Ischemia-reperfusion
Interleukin 8
Polymorphonuclear leukocytes
Lung transplantation
Objetivo

La generación local de citocinas es un factor patogénico en el daño por isquemia-reperfusión en la disfunción precoz del injerto. Este estudio analiza la expresión en tejido pulmonar de ARN mensajero de interleucina-8 (ARNm de IL-8) y su relación con los cambios intersticiales pulmonares en un modelo experimental de isquemia-reperfusión pulmonar normotérmica.

MATERIAL Y MÉTODOS

Se estudiaron 16 conejos de la raza Nueva Zelanda en 3 grupos de estudio: a) basal; b) isquemia (lóbulo inferior derecho tras isquemia de 1, 2 o 3 h), y c) reperfusión (lóbulos superior y medio derechos tras 1 h de isquemia y 1, 2 o 3 h de reperfusión). Se deter- minó la expresión del ARNm de IL-8 mediante transcripción inversa y reacción en cadena de la polimerasa y estudió la infiltración intersticial por polimorfonucleares (PMN). Para el análisis estadístico se empleó el test de la U de Mann-Whitney aceptando como significativo un valor de p < 0,05.

RESULTADOS

Durante el período de isquemia se observó respecto al basal elevación del ARNm de IL-8 al final de la primera hora (p = 0,009), pero no durante el resto del período isquémico. Los cambios intersticiales fueron mínimos. Durante la reperfusión los valores de ARNm de IL-8 fueron semejantes a los observados durante la isquemia, con una ligera elevación al final de segunda hora; no hubo diferencias significativas entre la primera, segunda y tercera horas. Hubo reclutamiento de PMN al inicio de la reperfusión (p = 0,014), sin observarse diferencias significativas en la segunda y tercera horas. Se objetivó un engrosamiento progresivo de los tabiques interalveolares y edema.

CONCLUSIONES

Los cambios en la expresión del ARNm de IL-8 durante la isquemia preceden a la infiltración intersticial de PMN durante la reperfusión, lo que señala una relación entre ambos procesos. La cuantificación del ARNm de IL-8 podría ser un procedimiento para el seguimiento diagnóstico de la disfunción precoz del injerto.

Palabras clave:
Isquemia-reperfusión
Interleucina-8
Leucocitos polimorfonucleares
Trasplante pulmonar
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REFERENCES
[1]
H Mal, M Dehoux, C Sleiman, J Boczkowski, G Leséche, R Pariente, et al.
Early release of proinflammatory cytokines after lung transplantation.
Chest, 113 (1998), pp. 645-651
[2]
mL Jones, MS Mulligan, CM Flory, PA Ward, JS Warren.
Potential role of monocyte chemoattractant protein 1/JE in monocyte/ macrophage-dependent IgA immune complex alveolitis in the rat.
J Immunol, 149 (1992), pp. 2147-2154
[3]
TP Shanley, H Schmal, RL Warner, E Schmid, HP Friedl, PA Ward.
Requirement for C-X-C chemokines (macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury.
J Immunol, 158 (1997), pp. 3439-3448
[4]
BV Naidu, B Krishnadasan, K Byrne, AL Farr, M Rosengart, ED Verrier, et al.
Regulation of chemokine expression by cyclosporine A in alveolar macrophages exposed to hypoxia and reoxygenation.
Ann Thorac Surg, 74 (2002), pp. 899-905
[5]
BF Meyer, J Lynch, EP Trulock, TJ Guthrie, JD Cooper, GA Patterson.
Lung transplantation: a decade of experience.
Ann Surg, 230 (1999), pp. 362-367
[6]
JM Schröder, U Mrowietz, E Christophers.
Purification and partial biologic characterization of a human lymphocyte derived peptide with potent neutrophil stimulating activity.
J Immunol, 140 (1988), pp. 3534-3540
[7]
AP Metinko, SL Kunkel, TJ Standiford, RM Strieter.
Anoxia-hyperoxia induces monocyte derived interleukin-8.
J Clin Invest, 90 (1992), pp. 791-798
[8]
I Nagahiro, M Aoe, M Yamashita, H Date, A Andou, N Shimizu.
EPC-K1 is effective in lung preservation in a ex vivo rabbit lung perfusion model.
Ann Thorac Surg, 63 (1997), pp. 954-959
[9]
M Haniuda, CM Dresler, S Hasegawa, GA Patterson, JD Cooper.
Changes in vascular permeability with ischemic time, temperature, and inspired oxygen fraction in isolated rabbit lungs.
Ann Thorac Surg, 57 (1994), pp. 708-714
[10]
M Haniuda, S Hasegawa, T Shiraishi, CM Dresler, JD Cooper, GA Patterson.
Effects of inflammation volume during lung preservation on pulmonary capillary permeability.
J Thorac Cardiovasc Surg, 112 (1996), pp. 85-93
[11]
JM Schröder, U Mrowietz, E Christophers.
Purification and partial biologic characterization of a human lymphocyte derived peptide with potent neutrophil stimulating activity.
J Immunol, 140 (1988), pp. 3534-3540
[12]
DW Harkin, AB Barros, K McCallion, M Hoper, MI Halliday, FC Campbell.
Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury.
Ann Surg, 234 (2001), pp. 233-244
[13]
AR Mueller, KP Platz, M Haak, H Undi, C Muller, E Kottgen, et al.
The release of cytokines, adhesion molecules and extracellular matrix parameters during and after reperfusion in human liver transplantation.
Transplantation, 62 (1996), pp. 1118-1126
[14]
N Sekido, N Mukaida, A Harada, I Nakanishi, Y Watanabe, K Matsushima.
Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8.
Nature, 365 (1993), pp. 654-657
[15]
T Sakuma, K Takahashi, N Ohya, O Kajikawa, TR Martin, AMA Matthay.
Ischemia-reperfusion lung injury in rabbits: mechanisms of injury and protection.
Am J Physiol Lung Cell Mol Physiol, 276 (1999), pp. L137-LL45
[16]
M de Perrot, Y Sekine, S Fischer, TK Waddell, K McRae, M Liu, et al.
Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation.
Am J Respir Crit Care Med, 165 (2002), pp. 211-215
[17]
AJ Fisher, SC Donnelly, N Hirani, C Haslett, RM Strieter, JH Dark, et al.
Elevated levels of interleukin-8 in donor lungs is associated with early graft failure after lung transplantation.
Am J Respir Crit Care Med, 63 (2001), pp. 259-265
[18]
H Kishima, SI Takeda, S Miyoshi, A Matsumura, M Minami, T Utsumi, et al.
Microvascular permeability of the non-heart beating rabbit lung after warm ischemia and reperfusion: role of neutrophil elastase.
Ann Thorac Surg, 65 (1998), pp. 913-918
[19]
R Adoumie, C Serrick, A Giaid, H Shennib.
Early cellular events in the lung allograft.
Ann Thorac Surg, 54 (1992), pp. 1071-1077
[20]
CN Steimle, TD Guynn, mL Morganroth, SF Bolling, K Carr, M Deeb.
Neutrophils are not necessary for ischemia-reperfusion lung injury.
Ann Thorac Surg, 53 (1992), pp. 64-73
[21]
M de Perrot, M Liu, TK Waddell, S Keshavjee.
Ischemia-reperfusion induced lung injury.
Am J Respir Crit Care Med, 167 (2003), pp. 490-511
[22]
AO Halldorsson, M Kronon, BS Allen, S Rahman, T Wang, M Layland, et al.
Controlled reperfusion prevents pulmonary injury after 24 hours of lung preservation.
Ann Thorac Surg, 66 (1998), pp. 877-885

This study was realized with the scientific help and the financiation of the Sociedad Española de Neumología y Cirugía Torácica. (SEPAR).

Copyright © 2007. Sociedad Española de Neumología y Cirugía Torácica (SEPAR)
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