The pathogenesis of pulmonary contusion: an open chest model in the rat.

BACKGROUND Chemokines direct leukocytes to areas of inflammation or injury. In general, CC chemokines (MCP-1, MIP-1alpha, RANTES) are chemoattractants for mononuclear cells and CXC (CINC-1, MIP-2alpha) for polymorphonuclear cells (PMNs). Herein we describe an open chest model of pulmonary contusion (PC) in a rodent (rat) and have identified a possible role for CC and CXC chemokines in the pathogenesis of PC. METHODS Sprague-Dawley rats (350 g) underwent thoracotomy. The exposed lung was struck with a piston at 5.2 m/s (150 J/M2). Blood, bronchoalveolar lavage (BAL), and lung tissue were collected at 3 hours and 24 hours after injury. PaO2/FiO2 (P/F) ratio was calculated at 15-minute intervals for 3 hours after contusion. Serum was evaluated for cytokine and chemokine expression using ELISA. Cell count/differential was performed on BAL, and lung tissue was obtained for histologic analysis, protein expression and wet to dry weights. Data are reported as pg/mL +/- SE. Data were analyzed using Student's t test to identify significant differences (p < or = 0.05 significant) between sham and injured animals. RESULTS Piston impact caused PC based upon morphologic and histologic criteria. BAL cell count and lung wet to dry weights were increased and P/F ratio was decreased after PC. Systemic levels of IL-ra, MCP-1, and the CXC chemokines MIP-2alpha and CINC-1 were significantly elevated at 3 hours when sham and injured animals were compared. All chemokines were found to be significantly elevated at 24 hours, consistent with the early PMN and subsequent mononuclear infiltration observed in the contused lung. Pulmonary expression of TNF-alpha, IL-1beta, CINC-1, MIP-2alpha, ICAM-1, and elastase were increased and activated systemic neutrophils showed increased CD-11b. CONCLUSION A model of PC is described in which innate inflammation is activated locally and systemically. Systemic levels of CC and CXC chemokines are increased after PC. This correlates with elevated PMN CD-11b expression, enhanced pulmonary ICAM-1 expression, and mononuclear and PMN infiltration into the lung and alveolar space. Elevated levels of CC and CXC chemokines are seen after PC and may be involved in the lung's inflammatory response to injury.

[1]  O. Trentz,et al.  Different pattern of local and systemic release of proinflammatory and anti-inflammatory mediators in severely injured patients with chest trauma. , 1996, The Journal of trauma.

[2]  P. Parsons,et al.  Circulating IL-1ra and IL-10 levels are increased but do not predict the development of acute respiratory distress syndrome in at-risk patients. , 1997, American journal of respiratory and critical care medicine.

[3]  P. Ward,et al.  Requirement and role of C5a in acute lung inflammatory injury in rats. , 1996, The Journal of clinical investigation.

[4]  Robert C. Thompson,et al.  Interleukin-1 receptor antagonist reduces mortality from endotoxin shock , 1990, Nature.

[5]  S. Moochhala,et al.  Chemokines in acute respiratory distress syndrome , 2005, American journal of physiology. Lung cellular and molecular physiology.

[6]  L. Kinzl,et al.  Cardiopulmonary, Histological, and Inflammatory Alterations After Lung Contusion in a Novel Mouse Model of Blunt Chest Trauma , 2003, Shock.

[7]  H. Redl,et al.  Does lung contusion affect both the traumatized and the noninjured lung parenchyma? A morphological and morphometric study in the pig. , 1995, The Journal of trauma.

[8]  P. Barton,et al.  Contrasting roles for tumor necrosis factor in the pathogeneses of IgA and IgG immune complex lung injury. , 1991, The American journal of pathology.

[9]  M. Lyte,et al.  Systemic and pulmonary effector cell function after injury* , 2002, Critical care medicine.

[10]  A. Lentsch,et al.  Regulation of experimental lung inflammation. , 2001, Respiration physiology.

[11]  J. Richardson,et al.  Lung bacterial clearance following pulmonary contusion. , 1979, Surgery.

[12]  H. Redl,et al.  LOCAL AND SYSTEMIC REACTIONS AFTER LUNG CONTUSION: AN EXPERIMENTAL STUDY IN THE PIG , 1998, Shock.

[13]  S. Cohn,et al.  Pulmonary contusion: review of the clinical entity. , 1997, The Journal of trauma.

[14]  P. Ward,et al.  Tumor necrosis factor α regulates in vivo intrapulmonary expression of ICAM-1 , 1993 .

[15]  H. Yagita,et al.  The α4β1 (Very Late Antigen (VLA)-4, CD49d/CD29) and α5β1 (VLA-5, CD49e/CD29) Integrins Mediate β2 (CD11/CD18) Integrin-Independent Neutrophil Recruitment to Endotoxin-Induced Lung Inflammation1 , 2001, The Journal of Immunology.

[16]  K. Davis,et al.  Mediator-dependent secondary injury after unilateral blunt thoracic trauma. , 1999, Shock.

[17]  S. Cohn,et al.  Experimental pulmonary contusion: review of the literature and description of a new porcine model. , 1996, The Journal of trauma.

[18]  J. Warren,et al.  Intrapulmonary interleukin 1 mediates acute immune complex alveolitis in the rat. , 1991, Biochemical and biophysical research communications.

[19]  J. Marshall,et al.  Inflammation, coagulopathy, and the pathogenesis of multiple organ dysfunction syndrome , 2001, Critical care medicine.

[20]  C. Smith,et al.  Role of β1 β2 integrins and ICAM-1 in lung injury after deposition of IgG and IgA immune complexes , 1993 .

[21]  T. Fabian,et al.  ARDS after pulmonary contusion: accurate measurement of contusion volume identifies high-risk patients. , 2001, The Journal of trauma.

[22]  K. Raghavendran,et al.  THE EVOLUTION OF ISOLATED BILATERAL LUNG CONTUSION FROM BLUNT CHEST TRAUMA IN RATS: CELLULAR AND CYTOKINE RESPONSES , 2005, Shock.

[23]  K. Marill,et al.  A current concept of trauma-induced multiorgan failure. , 2001, Annals of emergency medicine.

[24]  R. Thompson,et al.  The intratracheal administration of endotoxin and cytokines. III. The interleukin-1 (IL-1) receptor antagonist inhibits endotoxin- and IL-1-induced acute inflammation. , 1991, The American journal of pathology.

[25]  A. Sauaia,et al.  A 12-year prospective study of postinjury multiple organ failure: has anything changed? , 2005, Archives of surgery.

[26]  J. Paulauskis,et al.  Altered Neutrophil Trafficking During Sepsis1 , 2002, The Journal of Immunology.

[27]  T. Yednock,et al.  α9β1 Integrin is expressed on human neutrophils and contributes to neutrophil migration through human lung and synovial fibroblast barriers , 1999, Journal of leukocyte biology.

[28]  G. Downey,et al.  Proteases and lung injury , 2003, Critical care medicine.

[29]  T. Ulich,et al.  The intratracheal administration of endotoxin and cytokines. I. Characterization of LPS-induced IL-1 and TNF mRNA expression and the LPS-, IL-1-, and TNF-induced inflammatory infiltrate. , 1991, The American journal of pathology.

[30]  M. Burdick,et al.  The role of CXCR2/CXCR2 ligands in acute lung injury. , 2005, Current drug targets. Inflammation and allergy.

[31]  M. Keel,et al.  Pathophysiology of polytrauma. , 2005, Injury.

[32]  R. Hotchkiss,et al.  Molecular biology of multiple organ dysfunction syndrome: injury, adaptation, and apoptosis. , 2000, Surgical infections.

[33]  D. Prows,et al.  Acute lung injury: functional genomics and genetic susceptibility. , 2002, Chest.

[34]  T. Shimazu,et al.  Pulmonary contusion causes long-term respiratory dysfunction with decreased functional residual capacity. , 1990, The Journal of trauma.

[35]  J. Warren.  Disparate roles for TNF in the pathogenesis of acute immune complex alveolitis and dermal vasculitis. , 1991, Clinical immunology and immunopathology.

[36]  K. Raghavendran,et al.  A Rat Model for Isolated Bilateral Lung Contusion from Blunt Chest Trauma , 2005, Anesthesia and analgesia.

[37]  N. Matsuda,et al.  Systemic Inflammation and Disseminated Intravascular Coagulation in Early Stage of ALI and ARDS: Role of Neutrophil and Endothelial Activation , 2004, Inflammation.

[38]  K. Davis,et al.  Prostanoids: early mediators in the secondary injury that develops after unilateral pulmonary contusion. , 1998, The Journal of trauma.

[39]  P. G. Mullen,et al.  Acute lung injury: what have we learned from animal models? , 1993, The American journal of the medical sciences.

[40]  A. Balci,et al.  Unilateral Post-Traumatic Pulmonary Contusion: Findings of a Review , 2004, Surgery Today.

[41]  Variables affecting outcome in blunt chest trauma: flail chest vs. pulmonary contusion. , 1986 .