急性肺损伤患者中性粒细胞凋亡变化的研究

目的观察急性肺损伤(ALI)患者中性粒细胞(PMN)凋亡的发生以及与肺损伤的关系,并探讨其临床意义。方法对37例符合ALI诊断标准的患者,分离纯化肺灌洗液中的PMN,应用流式细胞术测定PMN凋亡、坏死、存活细胞比例及呼吸瀑发功能的变化,设健康对照组,并观察与乳酸脱氢酶(LDH)和胞浆游离Ca2 变化之间的关系。结果灌洗液中PMN凋亡比例显著降低,24h持续在低水平(P<0.05或P<0.01);各检测点活细胞增多(P<0.05或P<0.01);而灌洗液PMN的呼吸瀑发明显升高,8h达峰值,并持续升高(P<0.01)。灌洗液中LDH水平2～24h明显高于正常对照组(P<0.05或P<0.01);PMN胞浆游离Ca2 各检测点显著增高(P<0.05或P<0.01)。PMN凋亡与LDH水平有相关性(r=-0.7151,P<0.01),PMN凋亡与胞浆游离Ca2 水平有相关性(r=-0.6039,P<0.01)。结论ALI时PMN在肺组织中大量扣押,且正常的凋亡途径发生障碍,造成PMN持续处于激活状态及毒性内容物持续释放,与肺组织的损伤有密切关系,并且PMN凋亡延迟可能与LDH、胞浆游离Ca2 的升高有关。     

急性肺损伤病人中性粒细胞凋亡变化的研究

目的　观察急性肺损伤 (ALI)病人中性粒细胞 (PMN)凋亡的发生以及与肺损伤的关系 ,并探讨其临床意义。方法　对 37例符合ALI诊断标准的病人 ,分离纯化肺灌洗液中的PMN ,应用流式细胞术测定PMN凋亡、坏死、存活细胞比例及呼吸瀑发功能的变化 ,设健康对照组 ,并观察与乳酸脱氢酶 (LDH)和胞浆游离Ca2 变化之间的关系。结果　ALI病人肺灌洗液中PMN凋亡比例显著降低 ,2 4h持续在低水平 (P <0 0 5 ,P <0 0 1) ;各检测点活细胞增多 (P <0 0 5 ,P <0 0 1) ;而灌洗液PMN的呼吸瀑发明显升高 ,8h达峰值 ,并持续升高 (P <0 0 1)。灌洗液中LDH水平 2～ 2 4h明显高于正常对照组 (P <0 0 5 ,P<0 0 1) ;PMN胞浆游离Ca2 各检测点显著增高 (P <0 0 5 ,P <0 0 1)。PMN凋亡与LDH水平呈显著相关性 (r =- 0 715 1,P <0 0 1) ;PMN凋亡与胞浆游离Ca2 的浓度有显著的相关性 ( r=- 0 6 0 39,P <0 0 1)。结论　ALI时PMN在肺组织中大量扣押 ,且正常的凋亡途径发生障碍 ,造成PMN持续处于激活状态及毒性内容物的持续释放 ,与肺组织的损伤有密切关系 ,并且PMN凋亡延迟可能与LDH、胞浆游离Ca2 的升高有关     

大鼠内毒素血症时外周血及肺泡内中性粒细胞死亡方式及呼吸爆发

本研究观察大鼠内毒素血症时肺组织中及外周血多形核中性粒细胞（PMN）凋亡，坏死及功能改变的差异。采用Wistar大鼠20只。腹腔注射LPS（O55B5，5mg/kg)造成内毒素血症，给予LPS后2，4，8，12小时（每组5只动物）取血及支气管肺泡灌洗，密度梯度法分离PMN，用流式细胞仪测定凋亡和坏死比例以及呼吸爆发功能的改变，同时采用5只大鼠作为正常对照。结果显示，内毒素血症时外周血和支气管肺泡灌洗液中PMN凋亡细胞比例相似。但与对照相比，外周血PMN坏死比例明显增加，呼吸爆发能力明显受抑，而支气管肺泡灌洗液PMN坏死比例显减少，呼吸爆发能力显增强。结论：在内毒素血症时，扣押于肺组织中的PMN在凋亡和坏死上表现出与比例显减少，呼吸爆发能力显增强，结论：在内毒素血症时，扣押于肺组织中的PMN在凋亡和坏死上表现出与外周血PMN不同的改变，其结果是组织中PMN存活增加，并持续处于活化状态，这与PMN造成组织损伤有关。     

高速胸部撞击伤家兔中性粒细胞凋亡与肺损伤

目的:观察兔胸部高速撞击伤后中性粒细胞凋亡的发生与肺损伤的关系。方法:样品采集与处理于2003-05/2004-12,分别在解放军第四军医大学西京医院心脏外科实验室和胸部战创伤基础理论与临床实验室完成。实验选用健康国内本土兔30只,随机分为对照组5只,实验组25只。实验组动物应用呼吸心跳同步触发撞击机致伤右侧胸壁,压缩幅度20%,撞击质量5.7kg,撞击面积3.14cm2,弹丸速度(20.29±0.03)m/s。对照组不做撞击伤,其余处理同实验组。实验组于伤后4,12,24,48和72h分别处死动物5只(伤后4,12,24,48,72h组),留取支气管肺泡灌洗液及肺组织,应用膜连蛋白V-异硫氰基荧光素及碘化丙啶染色、流式细胞仪检测中性粒细胞凋亡,应用考马氏亮兰法、比色法测定总蛋白和白蛋白含量,肺组织苏木精-伊红染色及测定肺干湿重比值。结果:①伤后4,12,24,48,72h实验组支气管肺泡灌洗液凋亡的中性粒细胞比例明显低于对照组(63.1±7.6)%,(62.5±9.5)%,(64.2±7.1)%,(63.6±7.7)%,(61.5±8.5)%;(82.3±12.6)%,t=2.80～3.06,P<0.05。②伤后4,12,24,48,72h实验组肺干湿重比值明显低于对照组(0.32±0.10,0.29±0.03,0.26±0.05,0.25±0.01,0.21±0.03;0.48±0.07,t=2.90～7.94,P<0.05～0.01);伤后12,24,48,72h实验组肺通透指数明显高于对照组(1     

急性肺损伤炎性细胞凋亡异常及粒细胞集落刺激因子调控的研究

目的 探讨急性肺损伤时支气管肺泡灌洗液(BALF)中的中性粒细胞(PMN)凋亡发生规律及其与粒细胞集落刺激因子调控关系.方法 豚鼠30只,分为3组:组1为生理盐水正常对照组,组2为油酸致病组,组3为油酸+粒细胞集落刺激因子组.组2、组3分别由尾静脉注射油酸(0.12 ml/kg)造成豚鼠急性肺损伤模型.组1则注入生理盐水.组3在实验造模前2 d由皮下注射粒细胞集落刺激因子1.0μg/kg,1次/d.组1、组2、组3分别于注射后2 h用生理盐水进行全肺支气管肺灌洗,收集BALF.用梯度密度法离心收集PMN.用原位末端标记法检测BALF中PMN凋亡.结果 组2、组3和组1BALF中PMN凋亡百分比分别为(2.500±1.080)%、(3.500±0.850)%、(6.400±1.505)%.组2、组3较组1 BALF中PMN凋亡均显著降低(均P＜0.01).结论 急性肺损伤炎性细胞PMN凋亡延迟,PMN持续激活和释放毒性内容物与肺损伤有密切关系.粒细胞集落刺激因子能调控干预急性肺损伤时PMN凋亡延迟.     

高速胸部撞击伤家兔中性粒细胞凋亡与肺损伤

目的:观察兔胸部高速撞击伤后中性粒细胞凋亡的发生与肺损伤的关系.方法:样品采集与处理于2003-05/2004-12,分别在解放军第四军医大学西京医院心脏外科实验室和胸部战创伤基础理论与临床实验室完成.实验选用健康国内本土兔30只,随机分为对照组5只,实验组25只.实验组动物应用呼吸心跳同步触发撞击机致伤右侧胸壁,压缩幅度20%,撞击质量5.7kg,撞击面积3.14 cm^2,弹丸速度(20.29&;#177;0.03)m/s.对照组不做撞击伤,其余处理同实验组.实验组于伤后4,12,24,48和72 h分别处死动物5只(伤后4,12,24,48,72 h组),留取支气管肺泡灌洗液及肺组织,应用膜连蛋白V-异硫氰基荧光素及碘化丙啶染色、流式细胞仪检测中性粒细胞凋亡,应用考马氏亮兰法、比色法测定总蛋白和白蛋白含量,肺组织苏木精-伊红染色及测定肺干湿重比值.结果:①伤后4,12,24,48,72 h实验组支气管肺泡灌洗液凋亡的中性粒细胞比例明显低于对照组[(63.1&;#177;7.6)%,(62.5&;#177;9.5)%,(64.2&;#177;7.1)%,(63.6&;#177;7.7)%,(61.5&;#177;8.5)%;(82.3&;#177;12.6)%,t=2.80～3.06,P＜0.05].②伤后4,12,24,48,72 h实验组肺干湿重比值明显低于对照组(0.32&;#177;0.10,0.29&;#177;0.03,0.26&;#177;0.05,0.25&;#177;0.01,0.21&;#177;0.03;0.48&;#177;0.07,t=2.90～7.94,P＜0.05～0.01);伤后12,24,48,72 h实验组肺通透指数明显高于对照组(1.1&;#177;0.3,1.4&;#177;0.2,1.5&;#177;0.4,1.7&;#177;0.6;0.6&;#177;0.2,t=3.13～6.35,P＜0.05～0 01).结论:中性粒细胞凋亡抑制存在于创伤后肺损伤逐渐加重的过程中.     

上腹部手术患者外周血中性粒细胞凋亡及Bcl-2表达的变化

目的观察上腹部手术患者围手术期外周血中性粒细胞(PMN)凋亡及Bcl-2基因表达的变化.方法选择25例择期行上腹部手术患者,采用流式细胞术检测术前和术后不同时点外周血PMN凋亡及Bcl-2基因的表达.结果手术患者术前PMN凋亡率明显低于对照组,而Bcl-2的表达明显高于对照组.术后1、3、12、24 h PMN凋亡呈进行性下降,72 h时有所升高;Bcl-2基因的表达在术后1、3、12、24 h呈进行性升高,72 h时有所降低.结论手术应激可致手术患者外周血PMN凋亡延迟,可能是术后炎症反应的原因之一.Bcl-2基因表达上调是PMN凋亡延迟的分子机制之一.     

单侧胸部撞击致家兔对侧肺生物学标志的变化

目的研究单侧胸部撞击致家兔对侧肺损伤和早期炎症介质TNF-α在继发性肺损伤中的作用。方法选取新西兰大白兔48只,动物被随机分为正常对照组,伤后1、6、24 h各组。采用BIM-Ⅱ型生物撞击机复制单侧胸部撞击伤动物模型。在伤后1、6、24 h测定双肺生物学标志(肺湿/干重比、支气管肺泡灌洗液中性粒细胞、蛋白含量、肺微血管通透性)的变化,RT-PCR法测TNF-αmRNA在双侧肺组织中的表达。结果在伤后1、6、24 h与正常对照组相比双肺生物学标志均出现明显的变化(P＜0．05或P＜0．01), TNF-αmRNA在双侧肺组织中表达增加。结论单侧胸部撞击伤后,对侧肺生物学标志的改变和肺组织的病理变化程度一致,与对侧肺的机械性损伤因素和继发性炎症反应有关;TNF-αmRNA在肺组织中的表达增加,提示内源性炎症介质在继发性肺损伤的发生、发展过程中发挥重要作用。     

急性酒精中毒对创伤患者中性粒细胞凋亡与功能的影响

目的 探讨急性酒精中毒因素对创伤患者急诊期中性粒细胞(PMN)凋亡与功能的影响.方法 26例急性创伤患者依据创伤前是否有大量饮酒史及酒精浓度检测结果 分单纯创伤组(n=14),酒精中毒组(n=12),另选10例健康志愿者为对照组.于急诊期取血样,分离PMN并检测其凋亡、呼吸爆发功能及吞噬活性.结果 单纯创伤组和对照组PMN凋亡率差异无统计学意义(P>0.05);酒精中毒组PMN凋亡率大于前两组(P<0.01),与对照组比较,单纯创伤组PMN呼吸爆发功能指标明显升高,而吞噬活性指标则较低(P<0.01);酒精中毒组PMN呼吸爆发功能指标和吞噬活性指标明显低于其余两组(P<0.01).结论 创伤抑制PMN吞噬功能,使机体防御机能降低,酒精中毒因素通过促进PMN凋亡和抑制其吞噬和呼吸爆发功能,而加重这一免疫抑制过程,是创伤前酗酒或酒精中毒患者易并发感染的诱因之一.     

中性粒细胞凋亡对急性胰腺炎相关性肺损伤的影响

目的 研究中性粒细胞（PMN）在急性胰腺炎相关性肺损伤（PALl）中自发性凋亡的变化及与肺损伤的相关性，探讨PMN凋亡在这一过程中的病理意义。方法 采用5％牛磺胆酸钠（TAC）逆行胆胰管注射造成大鼠急性出血坏死性胰腺炎（AHNP）模型。将36只实验动物随机分为AHNP组、假手术组及地塞米松（DXM）治疗组，3h后处死动物。从支气管肺泡灌洗液分离PMN，在体外分别孵育1、3、6h后，以Annexin V／PI双染色法测定其自发性凋亡率。取肺组织测定肺湿／干比值、髓过氧化物酶（MPO）含量及肺通透性指数，研究自发性凋亡率与肺损伤之间的相关性。结果 三组大鼠支气管肺泡灌洗液PMN的自发性凋亡率随体外孵育时间的延长而逐渐增加；在3、6h时，AHNP组均低于假手术组及DXM治疗组，而肺温／干比值、MPO含量及肺通透性指数则高于后两组。AHNP组3h凋亡率与肺温／干比值、MPO含量及肺通透性指数呈负相关。结论 肺PMN凋亡减低与PALI大鼠模型肺损伤成负相关，同时伴有活性增强，是PALI发生的重要原因；DXM可减轻PALI，与其促进PMN凋亡。     

Cyclin-dependent kinase inhibition reduces lung damage in a mouse model of ventilator-induced lung injury

Mechanical ventilation (MV) has the potential to induce lung damage in healthy lungs or aggravate existing lung injury. Polymorphonuclear neutrophil (PMN) recruitment plays an important role in driving the inflammatory response in ventilator-induced lung injury (VILI). The cyclin-dependent kinase inhibitor r-roscovitine has been shown to induce apoptosis in PMNs. In this study, we investigated the potential of r-roscovitine treatment in reducing lung damage in a mouse model of VILI. Mice were tracheotomized and subjected to lung-protective MV with lower (～7.5 mL/kg) or lung-injurious MV with higher (～15 mL/kg) tidal volume (VT). R-roscovitine treatment enhanced apoptosis in PMNs in vitro. Ventilator-induced lung injury was associated with pulmonary PMN influx in low and high VT MV. During lung-injurious MV, r-roscovitine treatment reduced the number of PMNs and lowered levels of the lung damage markers RAGE (receptor for advanced glycation end products) and total immunoglobulin M in bronchoalveolar lavage fluid. R-roscovitine did not affect cytokine or chemokine levels in the bronchoalveolar space, neither during lung-protective nor lung-injurious MV. Thus, r-roscovitine treatment reduces lung damage in VILI, possibly dependent on increased apoptosis of PMNs.     

Pulmonary contusion induces alveolar type 2 epithelial cell apoptosis: role of alveolar macrophages and neutrophils

Alveolar type 2 (AT-2) cell apoptosis is an important mechanism during lung inflammation, lung injury, and regeneration. Blunt chest trauma has been shown to activate inflammatory cells such as alveolar macrophages (AMs) or neutrophils (polymorphonuclear granulocytes [PMNs]), resulting in an inflammatory response. The present study was performed to determine the capacity of different components/cells of the alveolar compartment (AMs, PMNs, or bronchoalveolar lavage [BAL] fluids) to induce apoptosis in AT-2 cells following blunt chest trauma. To study this, male Sprague-Dawley rats were subjected to either sham procedure or blunt chest trauma induced by a single blast wave. Various time points after injury (6 h to 7 d), the lungs were analyzed by immunohistochemistry, for AT-2 cells, or with antibodies directed against caspase 3, caspase 8, Fas, Fas ligand (FasL), BAX, and BCL-2. Bronchoalveolar lavage concentrations of TNF-alpha, IL-1beta, and soluble FasL were determined by enzyme-linked immunosorbent assay. Furthermore, cultures of AT-2 cells isolated from healthy rats were incubated with supernatants of AMs, PMNs, or BAL fluids obtained from either trauma or sham-operated animals in the presence or absence of oxidative stress. Annexin V staining or TUNEL (terminal deoxynucleotidyl transferase) assay was used to detect apoptotic AT-2 cells. Histological evaluation revealed that the total number of AT-2 cells was significantly reduced at 48 h following trauma. Fas, FasL, active caspase 8, and active caspase 3 were markedly up-regulated in AT-2 cells after chest trauma. BAX and BCL-2 did not show any significant changes between sham and trauma. IL-1beta, but not TNF-alpha, levels were markedly increased at 24 h after the injury, and soluble FasL concentrations were significantly enhanced at 6, 12, 24, and 48 h after the insult. Apoptosis of AT-2 cells incubated with supernatants from cultured AMs, isolated at 48 h following chest trauma was markedly increased when compared with shams. In contrast, no apoptosis was induced in AT-2 cells incubated with supernatants of activated PMNs or BAL fluids of traumatized animals. In summary, blunt chest trauma induced apoptosis in AT-2 cells, possibly involving the extrinsic death receptor pathway. Furthermore, mediators released by AMs appeared to be involved in the induction of AT-2 cell apoptosis.     

Entry of gut lymph into the circulation primes rat neutrophil respiratory burst in hemorrhagic shock.

OBJECTIVE: Endothelial cell injury by polymorphonuclear neutrophil (neutrophil [PMN]) respiratory burst after trauma and hemorrhagic shock (T/HS) predisposes subjects to acute respiratory distress syndrome and multiple organ failure. T/HS mesenteric lymph injures endothelial cell and lymph duct ligation (LDL) before T/HS prevents pulmonary injury. We investigated the role of mesenteric lymph in PMN priming by T/HS. DESIGN: Prospective experiment in rats. SETTING: University hospital laboratory. SUBJECTS: Adult male rats. INTERVENTIONS: Mesenteric lymph was obtained from rats undergoing T/HS (30 mm Hg, 90 mins) or sham shock (T/SS). Plasma was harvested from uninstrumented control (UC), T/HS, T/SS, and T/HS+LDL rats. PMNs were isolated from UC, T/HS, and T/HS+LDL rats. MEASUREMENTS AND MAIN RESULTS: PMNs from UC rats were incubated in buffer, 1% T/HS lymph, and 1% T/SS lymph. PMNs from UC rats were incubated in UC, T/HS, T/SS, and T/HS+LDL plasma. PMN respiratory burst was initiated by using macrophage inflammatory protein (MIP)-2/platelet-aggregating factor (PAF) or phorbol myristate acetate. Cytosolic calcium ([Ca2+]i) responses to MIP-2/PAF were assayed in PMN from UC, T/HS, and T/HS+LDL rats. PMN preincubated in T/HS lymph showed significant elevations in MIP/PAF-elicited respiratory burst compared with T/HS lymph or buffer only (p <.05; analysis of variance/Tukey's test). T/HS lymph incubation also increased (p <.05) phorbol myristate acetate elicited respiratory burst compared with buffer or T/SS. Preincubation in T/HS plasma increased MIP-2/PAF-elicited respiratory burst (p <.05) compared with UC or T/SS plasma. LDL blocked T/HS priming of respiratory burst. Control PMN [Ca2+]i responses to MIP-2 and PAF were low. T/SS PMN were significantly more responsive, but the T/HS PMN showed still higher responses (p <.01). LDL reversed the priming of [Ca2+]i responses by T/HS (p <.01). CONCLUSIONS: PMNs are primed by T/HS lymph but not T/SS lymph and by T/HS plasma but not T/SS plasma. LDL before shock prevents T/HS plasma from priming PMN. The magnitude of respiratory burst found here paralleled the [Ca2+]i responses seen to receptor dependent initiating agonists. Mesenteric lymph is both necessary and sufficient to prime PMN after T/HS in the rat, and it primes PMN in part by enhancing [Ca2+]i responses to G-protein coupled chemoattractants. Mesenteric lymph mediates postshock PMN dysfunction.     

Critical role of endothelial CXCR2 in LPS-induced neutrophil migration into the lung

In models of acute lung injury, CXC chemokine receptor 2 (CXCR2) mediates migration of polymorphonuclear leukocytes (PMNs) into the lung. Since CXCR2 ligands, including CXCL1 and CXCL2/3, are chemotactic for PMNs, CXCR2 is thought to recruit PMNs by inducing chemotactic migration. In a model of PMN recruitment to the lung, aerosolized bacterial LPS inhalation induced PMN recruitment to the lung in wild-type mice, but not in littermate CXCR2-/- mice. Surprisingly, lethally irradiated wild-type mice reconstituted with CXCR2-/- BM still showed about 50% PMN recruitment into bronchoalveolar lavage fluid and into lung interstitium, but CXCR2-/- mice reconstituted with CXCR2-/- BM showed no PMN recruitment. Conversely, CXCR2-/- mice reconstituted with wild-type BM showed a surprisingly large defect in PMN recruitment, inconsistent with a role of CXCR2 on PMNs alone. Cell culture, immunohistochemistry, flow cytometry, and real-time RT-PCR were used to show expression of CXCR2 on pulmonary endothelial and bronchial epithelial cells. The LPS-induced increase in lung microvascular permeability as measured by Evans blue extravasation required CXCR2 on nonhematopoietic cells. Our data revealed what we believe to be a previously unrecognized role of endothelial and epithelial CXCR2 in LPS-induced PMN recruitment and lung injury.     

Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation.

Tumor necrosis factor (TNF alpha), both by direct action and by trafficking cells of the immune system, is implicated in cardiopulmonary derangements and PMN-mediated microvascular injury associated with gram-negative sepsis. We examined the effects of pretreatment with a monoclonal antibody to TNF alpha on PMN function, hemodynamic derangements, and alveolar capillary membrane damage in a septic porcine model. Anti-TNF alpha profoundly improved hemodynamic consequences in this model. Reduction in PMN CD11/18 receptor expression, lung myeloperoxidase activity, and attenuation of peripheral neutropenia (all P < 0.05) indicate that pretreatment significantly reduced lung sequestration of PMNs seen in septic controls. In contrast, PMN oxygen radical (O2-) generation was not significantly different from unprotected septic animals. Despite the presence of circulating PMNs primed for O2- burst, alveolar capillary membrane damage, assessed by bronchoalveolar lavage protein content and arterial PO2 was markedly attenuated in the treatment group (P < 0.05). We conclude that anti-TNF alpha suppresses systemic hemodynamic actions of TNF alpha. Further, it prevents upregulation of PMN adhesion receptors inhibiting PMN/endothelial cell interaction. This prevents formation of a "microenvironment," protected from circulating oxidant scavengers, into which sepsis-activated PMNs release their toxic products. Pretreatment with anti-TNF alpha monoclonal antibody thus affords global protection in porcine Gram-negative sepsis.     

Role of activated neutrophils in chest trauma-induced septic acute lung injury

More than 50% of severely injured patients have chest trauma. Second insults frequently result in acute lung injury (ALI), with sepsis being the main underlying condition. We aimed to develop a standardized, reproducible, and clinically relevant double-hit mouse model of ALI induced by chest trauma and polymicrobial sepsis and to investigate the pathophysiologic role of activated neutrophils. Lung contusion was applied to C57Bl/6 mice via a focused blast wave. Twenty-four hours later, sepsis was induced by cecal ligation and puncture. For polymorphonuclear leukocyte (PMN) depletion, animals received intravenous injections of PMN-depleting antibody. In response to blunt chest trauma followed by sepsis as well as after sepsis alone, a significant local and systemic inflammatory response with increased cytokine/chemokine levels in lung and plasma was observed. In contrast, lung apoptosis was markedly elevated only after a double hit. Intra-alveolar neutrophils and total bronchoalveolar lavage protein concentrations were markedly increased following isolated chest trauma or the combined insult, but not after sepsis alone. Lung myeloperoxidase activity was enhanced only in response to the double hit accompanied by histological disruption of the alveolar architecture, lung congestion, and marked cellular infiltrates. Neutrophil depletion significantly diminished lung interleukin 1β and interleukin 6 concentrations and reduced the degree of septic ALI. Here we have established a novel and highly reproducible mouse model of chest trauma-induced septic ALI characterizing a clinical relevant double-hit scenario. In particular, the depletion of neutrophils substantially mitigated the extent of lung injury, indicating a pathomechanistic role for neutrophils in chest trauma-induced septic ALI.