Acute respiratory distress syndrome induced by H9N2 virus in mice

H9N2 avian influenza viruses have repeatedly caused infections in swine and humans in some countries. The purpose of the present study was to evaluate the pulmonary pathology caused by H9N2 viral infection in mice. Six- to eight-week-old BALB/c mice were infected intranasally with 1 × 10⁴ MID₅₀ of A/Chicken/Hebei/4/2008(H9N2) virus. Clinical signs, pathological changes and viral replication in lungs, arterial blood gas, and cytokines in bronchoalveolar lavage fluid (BALF) were observed at different time points after infection. A control group was infected intranasally with noninfectious allantoic fluid. H9N2-infected mice exhibited severe respiratory syndrome, with a mortality rate of 60%. Gross observations showed that infected lungs were highly edematous. Major histopathological changes in infected lungs included diffuse pneumonia and alveolar damage, with neutrophil-dominant inflammatory cellular infiltration, interstitial and alveolar edema, hemorrhage, and severe bronchiolitis/peribronchiolitis. In addition, H9N2 viral infection resulted in severe progressive hypoxemia, lymphopenia, and a significant increase in neutrophils, tumor necrosis factor-α and interleukin-6 in BALF. The features described above satisfy the criteria for acute respiratory distress syndrome (ARDS). Our data show that H9N2 viral infection resulted in ARDS in mice, and this may facilitate studies of the pathogenesis of future potential H9N2 disease in humans.     

Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis

Complications of acute respiratory distress syndrome (ARDS) are common among critically ill patients infected with highly pathogenic influenza viruses. Macrophages and neutrophils constitute the majority of cells recruited into infected lungs, and are associated with immunopathology in influenza pneumonia. We examined pathological manifestations in models of macrophage- or neutrophil-depleted mice challenged with sublethal doses of influenza A virus H1N1 strain PR8. Infected mice depleted of macrophages displayed excessive neutrophilic infiltration, alveolar damage, and increased viral load, later progressing into ARDS-like pathological signs with diffuse alveolar damage, pulmonary edema, hemorrhage, and hypoxemia. In contrast, neutrophil-depleted animals showed mild pathology in lungs. The brochoalveolar lavage fluid of infected macrophage-depleted mice exhibited elevated protein content, T1-α, thrombomodulin, matrix metalloproteinase-9, and myeloperoxidase activities indicating augmented alveolar-capillary damage, compared to neutrophil-depleted animals. We provide evidence for the formation of neutrophil extracellular traps (NETs), entangled with alveoli in areas of tissue injury, suggesting their potential link with lung damage. When co-incubated with infected alveolar epithelial cells in vitro, neutrophils from infected lungs strongly induced NETs generation, and augmented endothelial damage. NETs induction was abrogated by anti-myeloperoxidase antibody and an inhibitor of superoxide dismutase, thus implying that NETs generation is induced by redox enzymes in influenza pneumonia. These findings support the pathogenic effects of excessive neutrophils in acute lung injury of influenza pneumonia by instigating alveolar-capillary damage.     

Fas and fas ligand are up-regulated in pulmonary edema fluid and lung tissue of patients with acute lung injury and the acute respiratory distress syndrome

Apoptosis mediated by Fas/Fas ligand (FasL) interaction has been implicated in human disease processes, including pulmonary disorders. However, the role of the Fas/FasL system in acute lung injury (ALI) and in the acute respiratory distress syndrome (ARDS) is poorly defined. Accordingly, we investigated both the soluble and cellular expression of the Fas/FasL system in patients with ALI or ARDS. The major findings are summarized as follows. First, the soluble expression of the Fas/FasL system was assessed in undiluted pulmonary edema fluid and simultaneous plasma. Pulmonary edema fluid obtained from patients with ALI or ARDS (n = 51) had significantly higher concentrations of both soluble Fas (27 ng/ml; median; P < 0.05) and soluble FasL (0.125 ng/ml; P < 0.05) compared to control patients with hydrostatic pulmonary edema (n = 40; soluble Fas, 12 ng/ml; soluble FasL, 0.080 ng/ml). In addition, the concentrations of both soluble Fas and soluble FasL were significantly higher in the pulmonary edema fluid of the patients with ALI or ARDS compared to simultaneous plasma samples (soluble Fas, 16 ng/ml; soluble FasL, 0.058 ng/ml; P < 0.05), indicating local release in the lung. Higher soluble Fas concentrations were associated with worse clinical outcomes. Second, cellular expression of the Fas/FasL system was assessed by semiquantitative immunofluorescence microscopy in lung tissue obtained at autopsy from a different set of patients. Both Fas and FasL were immunolocalized to a greater extent in the patients who died with ALI or ARDS (n = 10) than in the patients who died without pulmonary disease (n = 10). Both proteins were co-expressed by epithelial cells that lined the alveolar walls, as well as by inflammatory cells and sloughed epithelial cells that were located in the air spaces. Semiquantitative immunohistochemistry showed that markers of apoptosis (terminal dUTP nick-end labeling, caspase-3, Bax, and p53) were more prevalent in alveolar wall cells from the patients who died with ALI or ARDS compared to the patients who died without pulmonary disease. These findings indicate that alveolar epithelial injury in humans with ALI or ARDS is in part associated with local up-regulation of the Fas/FasL system and activation of the apoptotic cascade in the epithelial cells that line the alveolar air spaces.     

Pulmonary pathology in patients associated with scrub typhus

AIMS: Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi. Severe cases resulting in mortality from this disease have rarely been reported. We present two scrub typhus cases (a man and a girl) who died of acute respiratory distress syndrome (ARDS). METHODS: Autopsies were performed. Histopathological and immunohistochemical stains were employed using specific antibody for O. tsutsugamushi and inducible nitric oxide synthase (iNOS). RESULTS: These subjects developed respiratory distress shortly after admission, and expired following respiratory failure. At autopsy, generalised lymphadenopathy was observed. The lung weight was about two-fold the normal value. Gross inspection revealed oedematous and haemorrhagic lungs. Microscopic examination revealed diffuse alveolar damage with hyaline membrane formation and interstitial pneumonitis with infiltration of inflammatory cells. Immunohistochemical stain showed O. tsutsugamushi antigen depositions in the endothelial cells. We also demonstrated iNOS in the alveolar macrophages and lung tissue debris in both cases. CONCLUSION: Scrub typhus is usually a mild infectious disease. Our cases present the most dramatic example of sudden death due to ARDS in a short period of time. The clinical investigation and analysis suggest direct endothelial cell invasion of the organism and marked iNOS expression may be involved in the pathogenesis of ARDS associated with scrub typhus.     

干细胞旁分泌效应在ALI/ARDS治疗中的研究进展

急性肺损伤(acute lung injury,ALI)以及它的严重形式——急性呼吸窘迫综合征(acute respiratorydistress syndrome,ARDS)是危重病人发病和死亡的重要原因之一,最近2个世纪以来,死亡率仍在36%～44%左右。ALI/ARDS的病因众多,发病机制十分复杂,涉及的环节多,受损的靶细胞多,主要涉及的环节有:炎症反应失控、细胞损伤与修复、细胞凋     

Low-dose Interferon-α Treatment Improves Survival and Inflammatory Responses in a Mouse Model of Fulminant Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of symptoms, therapeutic strategies for this pathologic condition are still poorly developed. Interferon (IFN)-α is well known as an antiviral cytokine and low-dose IFN-α has been reported to show antiinflammatory effects. Therefore, we investigated how this cytokine affected ARDS in a mouse model. C57BL/6 mice received sequential intratracheal administration of α-galactosylceramide (α-GalCer) and lipopolysaccharide (LPS), which resulted in the development of fulminant ARDS. These mice were then treated intranasally with IFN-α and their survival, lung weight, pathological findings, and cytokine production were evaluated. Administration of low-dose IFN-α prolonged survival of fulminant ARDS mice, but higher doses of IFN-α did not. Histological analysis showed that low-dose IFN-α treatment improved findings of diffuse alveolar damage in fulminant ARDS mice, which was associated with reduction in the wet/dry (W/D) lung weight ratio. Furthermore, IFN-γ production in the lungs was significantly reduced in IFN-α-treated mice, compared with control mice, but tumor necrosis factor (TNF)-α production was almost equivalent for both groups. Low-dose IFN-α shows antiinflammatory and therapeutic effects in a mouse model of fulminant ARDS, and reduced production of IFN-γ in the lung may be involved in the beneficial effect of this treatment.     

CD44 as a novel target for treatment of staphylococcal enterotoxin B-induced acute inflammatory lung injury

Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). In the current study, we investigated the role of CD44 in ALI/ARDS. Intranasal exposure of CD44 wild-type mice to SEB led to a significant increase in the expression of CD44 on lung mononuclear cells. CD44 knockout mice developed significantly reduced SEB-induced ALI/ARDS, through reduced inflammatory cytokine production and reduced lung inflammatory cells, compared to similarly treated CD44 wild-type mice. Mechanistically, deletion of CD44 altered SEB-induced cytokine production in the lungs and reduced the ability of SEB-exposed leukocytes to bind to lung epithelial cells. Finally, treatment of SEB-exposed mice with anti-CD44 mAbs led to significant reduction in vascular permeability, reduction in cytokine production, and prevented inflammatory cell infiltration in the lungs. Together, these results suggest the possibility of targeting CD44 for the treatment of SEB-induced ALI/ARDS.     

Involvement of high mobility group box 1 and the therapeutic effect of recombinant thrombomodulin in a mouse model of severe acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is accompanied by severe lung inflammation induced by various diseases. Despite the severity of the symptoms, therapeutic strategies have been ineffective. High mobility group box 1 (HMGB1), which was identified originally as a DNA binding protein, has been proposed as a mediator of acute lung injury. In addition to its anti‐coagulant activity, recombinant thrombomodulin (rTM) possesses an ability to suppress the inflammatory response through neutralizing HMGB1. T regulatory (T_reg) cells in the lungs are reported to modify innate immune responses during resolution of acute lung injury. In the present study, we investigated the therapeutic effect of rTM, and the contribution of T_reg cells to this effect, in a mouse model of severe ARDS. C57BL/6 mice received sequential intratracheal administration of α‐galactosylceramide (α‐GalCer) and lipopolysaccharide (LPS), which resulted in the development of severe ARDS. HMGB1 levels in the lungs increased to a higher level in ARDS mice compared to those in mice treated with LPS alone. HMGB1 was expressed in the infiltrating neutrophils and macrophages in lungs. T_reg cells were reduced significantly in the lungs of ARDS mice compared to those in mice treated with LPS alone. rTM administration prolonged the survival time and ameliorated the development of ARDS, which was associated with increased T_reg cells and synthesis of interleukin (IL)‐10 and transforming growth factor (TGF)‐β in the lungs. These results suggest that HMGB1 is involved in the development of severe ARDS and rTM shows therapeutic effects through promoting the accumulation of T_reg cells at the inflammatory sites.     

Increased expression of 11 beta-hydroxysteroid dehydrogenase type 2 in the lungs of patients with acute respiratory distress syndrome

We examined the immunohistochemical distribution of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2), the enzyme responsible for the conversion of bioactive glucocorticoids to their receptor-inactive forms, in lung tissue obtained at autopsy from 14 patients who had died due to acute respiratory distress syndrome (ARDS). We found positive immunoreactivity for 11 beta-HSD2 in 13 cases. The cells expressing 11 beta-HSD2 in the alveolar wall were positive for surfactant apoprotein-A as well as cytokeratin. Immunoreactivity for 11 beta-HSD2 was also detected in the CD68+ cells, which were found in the alveolar spaces. All patients had been treated with glucocorticoids for ARDS and/or the underlying diseases. There was no statistically significant correlation between the use of glucocorticoids and 11 beta-HSD2 immunoreactivity in the alveolar wall (P = 0.0729). However, expression of grade + + was found in three out of five patients who received dexamethasone pulse therapy at relatively large doses, as well as in three other patients treated with prednisolone for a long period of time for the underlying disease. An increase in the expression of 11 beta-HSD2 may result in faster glucocorticoid breakdown in lung cells in patients with ARDS. Impaired glucocorticoid availability in the lungs of such patients may explain, in part, the fact that glucocorticoid therapy does not always rescue patients with ARDS.     

Mouse-passaged severe acute respiratory syndrome-associated coronavirus leads to lethal pulmonary edema and diffuse alveolar damage in adult but not young mice

Advanced age is a risk factor of severe acute respiratory syndrome (SARS) in humans. To understand its pathogenesis, we developed an animal model using BALB/c mice and the mouse-passaged Frankfurt 1 isolate of SARS coronavirus (SARS-CoV). We examined the immune responses to SARS-CoV in both young and adult mice. SARS-CoV induced severe respiratory illness in all adult, but not young, mice on day 2 after inoculation with a mortality rate of 30 to 50%. Moribund adult mice showed severe pulmonary edema and diffuse alveolar damage accompanied by virus replication. Adult murine lungs, which had significantly higher interleukin (IL)-4 and lower IL-10 and IL-13 levels before infection than young murine lungs, rapidly produced high levels of proinflammatory chemokines and cytokines known to induce macrophage and neutrophil infiltration and activation (eg, tumor necrosis factor-alpha). On day 2 after inoculation, young murine lungs produced not only proinflammatory cytokines but also IL-2, interferon-gamma, IL-10, and IL-13. Adult mice showed early and acute excessive proinflammatory responses (ie, cytokine storm) in the lungs after SARS-CoV infection, which led to severe pulmonary edema and diffuse alveolar damage. Intravenous injection with anti-tumor necrosis factor-alpha antibody 3 hours after infection had no effect on SARS-CoV infection. However, intraperitoneal interferon-gamma injection protected adult mice from the lethal respiratory illness. The experimental model described here may be useful for elucidating the pathophysiology of SARS and for evaluating therapies to treat SARS-CoV infection.     

The discovery of angiotensin-converting enzyme 2 and its role in acute lung injury in mice

During several months of 2002, severe acute respiratory syndrome (SARS) caused by SARS-coronavirus (SARS-CoV) spread rapidly from China throughout the world, causing more than 800 deaths due to the development of acute respiratory distress syndrome (ARDS), which is the severe form of acute lung injury (ALI). Interestingly, a novel homologue of angiotensin-converting enzyme, termed angiotensin-converting enzyme 2 (ACE2), has been identified as a receptor for SARS-CoV. Angiotensin-converting enzyme and ACE2 share homology in their catalytic domain and provide different key functions in the renin-angiotensin system (RAS). Angiotensin-converting enzyme cleaves angiotensin I to generate angiotensin II, which is a key effector peptide of the system and exerts multiple biological functions, whereas ACE2 reduces angiotensin II levels. Importantly, our recent studies using ACE2 knockout mice have demonstrated that ACE2 protects murine lungs from ARDS. Furthermore, SARS-CoV infections and the Spike protein of the SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice worsens acute lung failure in vivo, which can be attenuated by blocking the renin-angiotensin pathway, suggesting that the activation of the pulmonary RAS influences the pathogenesis of ALI/ARDS and SARS.     

Respiratory Reovirus 1/L Induction of Diffuse Alveolar Damage: Pulmonary Fibrosis Is Not Modulated by Corticosteroids in Acute Respiratory Distress Syndrome in Mice

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage (DAD) secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult. We have previously described a unique animal model in which CBA/J mice infected with reovirus 1/L develop ARDS. This model recapitulates the histopathological changes observed in human ARDS, which consist of the overlapping phases of exudation, including the formation of hyaline membranes, regeneration, and healing via repair with fibrosis. In this report, we show that the development of DAD in the acute phase of the disease and intraalveolar fibrosis in the late phase of the disease was not modulated by treatment with methylprednisolone (MPS). In the presence or absence of MPS, the majority of cells infiltrating the lungs after reovirus 1/L infection were polymorphonuclear leukocytes and macrophages. A number of key proinflammatory and anti-inflammatory cytokines/chemokines that are observed in the BAL fluid of ARDS patients were also found in the lungs of mice after reovirus 1/L infection and were not modulated by MPS. These include interferon-γ, interleukin-10, and monocyte chemoattractant protein. The histopathology, cytokine/chemokine expression, and response to corticosterids in reovirus 1/L-induced ARDS are similar to what is observed in human patients, making this a clinically relevant model.     

Respiratory reovirus 1/L induction of diffuse alveolar damage: a model of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome that is characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult. In this report we describe a unique animal model in which CBA/J mice infected with reovirus serotype 1, strain Lang develop ARDS. This model recapitulates the histopathological changes observed in human ARDS, which consists of the overlapping phases of exudation including the formation of hyaline membranes, regeneration, and healing via resolution and/or repair with fibrosis. While the consequences of a number of infectious and noninfectious insults in various animal systems have been developed as models of human ARDS, they are models of acute lung injury and are of short-term duration. Therefore, they do not recapitulate all of the clinical and pathological phases observed in human ARDS. Thus, study of the cellular and molecular factors involved in these distinct phases of the disease have been limited. Reovirus 1/L infection of CBA/J mice will allow investigations of the pathophysiology of ARDS as it progresses from the initial stages of edema and neutrophilia to fibrotic lesion development in late stages.     

Regulatory T-cells promote pulmonary repair by modulating T helper cell immune responses in lipopolysaccharide-induced acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) induces a strong local infiltration of regulatory T-cells (Tregs) in the lungs. However, at present, there remains a lack of adequate evidence showing the direct effect of Tregs on pulmonary repair and the related mechanisms of ARDS. Therefore, in this project, we studied the impact of Tregs on lipopolysaccharide (LPS)-induced ARDS and pulmonary inflammation. Surprisingly, we found that depletion of Tregs by injection of PC61 anti-CD25 antibody not only interfered with the inflammation resolution, such as inhibited total cell infiltration into the alveolar space, downregulated neutrophils, upregulated macrophages, but also impaired pulmonary epithelium and endothelial cell proliferation. Consistent with the attenuation of pulmonary repair, we found that the Th1 and Th17 immune responses were also impaired in Treg-depleted mice, suggesting that the presence of Tregs is vital for tissue repair, as Tregs modulate and promote the Th immune response in LPS-induced pulmonary inflammation.     

Heterogeneous expression of cell adhesion molecules by endothelial cells in ARDS

ARDS (acute respiratory distress syndrome) can be associated with septic shock and multiple organ failure caused by an uncontrolled systemic inflammatory response to Gram-negative bacterial infection. While in animal models the key role of the endothelial adhesion molecules ICAM-1, E-selectin, and VCAM in ARDS has been extensively studied, there are scarcely any corresponding pathomorphological studies of human lung tissue. Hence, little is known about whether there is a comparable, or even heterogeneous, expression pattern of these molecules in the human pulmonary vasculature. This study was therefore undertaken to investigate the immunohistochemical expression of the constitutively expressed PECAM (CD31) and the inducible molecules ICAM-1, E-selectin, and VCAM in ARDS lungs from patients who had died in septic shock induced by Gram-negative bacteria. While in all specimens (ARDS and normal lungs) there was homogeneous strong expression of PECAM in all vessels, ICAM-1 was clearly up-regulated in ARDS lungs. E-selectin and VCAM were not expressed by endothelial cells (ECs) in normal lungs, but in ARDS lungs there was strong expression of both molecules in larger vessels, while in the capillaries there was only mosaic-like weak expression of a few ECs. This immunohistochemical investigation demonstrates the induction and up-regulation of adhesion molecules in human ARDS lungs, comparable to that described in animal models. There is also markedly heterogeneous expression of E-selectin and VCAM, indicating toporegional differences in the function of pulmonary ECs.     

2019新型冠状病毒导致的致命肺渗漏的病理生理学机制和防治策略:兼论血透的应用与依据

自2019年12月爆发以来,2019新型冠状病毒已在全球造成2872人死亡(截至2020年2月28日),并且有超过8000名患者仍处于严重状况。该病毒和由该病毒引起的医疗状况被分别命名为SARS-CoV-2(severe acute respiratory syndrome coronavirus-2)和COVID-19(coronavirus disease 2019)。虽然已经广泛应用了抗病毒、对症和功能支持性疗法,每天仍有大量患者死于该病毒感染。SARS-CoV-2主要通过2型肺泡上皮细胞上的血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)首先感染肺,其最常见的致命并发症是急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)[1]。     

Vascular immunotargeting of glucose oxidase to the endothelial antigens induces distinct forms of oxidant acute lung injury: targeting to thrombomodulin, but not to PECAM-1, causes pulmonary thrombosis and neutrophil transmigration

Oxidative endothelial stress, leukocyte transmigration, and pulmonary thrombosis are important pathological factors in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Vascular immunotargeting of the H(2)O(2)-generating enzyme glucose oxidase (GOX) to the pulmonary endothelium causes an acute oxidative lung injury in mice.(1) In the present study we compared the pulmonary thrombosis and leukocyte transmigration caused by GOX targeting to the endothelial antigens platelet-endothelial cell adhesion molecule (PECAM) and thrombomodulin (TM). Both anti-PECAM and anti-TM delivered similar amounts of (125)I-GOX to the lungs and caused a dose-dependent, tissue-selective lung injury manifested within 2 to 4 hours by high lethality, vascular congestion, polymorphonuclear neutrophil (PMN) sequestration in the pulmonary vasculature, severe pulmonary edema, and tissue oxidation, yet at an equal dose, anti-TM/GOX inflicted more severe lung injury than anti-PECAM/GOX. Moreover, anti-TM/GOX-induced injury was accompanied by PMN transmigration in the alveolar space, whereas anti-PECAM/GOX-induced injury was accompanied by PMN degranulation within vascular lumen without PMN transmigration, likely because of PECAM blockage. Anti-TM/GOX caused markedly more severe pulmonary thrombosis than anti-PECAM/GOX, likely because of TM inhibition. These results indicate that blocking of specific endothelial antigens by GOX immunotargeting modulates important pathological features of the lung injury initiated by local generation of H(2)O(2) and that this approach provides specific and robust models of diverse variants of human ALI/ARDS in mice. In particular, anti-TM/GOX causes lung injury combining oxidative, prothrombotic, and inflammatory components characteristic of the complex pathological picture seen in human ALI/ARDS.     

Inhaled Aerosolized Insulin: A “Topical” Anti-inflammatory Treatment for Acute Lung Injury and Respiratory Distress Syndrome?

Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are forms of pulmonary edema that result from robust local and systemic inflammatory states, such as sepsis. The morbidity and mortality associated with ALI and ARDS are significant and the treatment of these conditions presents a formidable challenge. Controlling hyperglycemia with insulin is a core component of patient management in the critically ill. Insulin treatment also exerts beneficial metabolic effects beyond glucose control, as well as non-metabolic effects, in insulin-resistant states. For instance, insulin inhibits NF-κB—dependent synthesis of pro-inflammatory factors and attenuates production of ROS. Indeed, intravenous administration of insulin ameliorates pulmonary injury and dysfunction in the LPS model of ALI. Most recently, an inhalable insulin formulation was shown to effectively reduce glucose concentrations with minimal impact on long-term pulmonary function. We propose that administering inhalable insulin to hyperglycemic ALI/ARDS patients could directly reduce alveolar inflammation while reducing circulating glucose levels.     

Immunohistochemical expression of MPO,CD163 and VEGF in inflammatory cells in acute respiratory distress syndrome: a case report

Acute respiratory distress syndrome (ARDS) is a serious medical condition occurring in patients with polytrauma, pulmonary or non-pulmonary sepsis, pneumonia and many other circumstances. It causes inflammation of the lung parenchyma leading to impaired gas exchange with a systemic release of inflammatory mediators, causing consequential lung tissue injury, hypoxemia and frequently multiple organ failure. The aim of current study was to describe expression of inflammatory markers (myeloperoxidase, CD163 and vascular endothelial growth factor) by the cells in acute phase of ARDS. The lung samples of a 20-year-old man who had suffered a serious motorbike accident were obtained for histological examination. He died on the seventh day as a consequence of respiratory failure. Our results imply that expression of CD163 was restricted to activated alveolar macrophages and monocytes. Immunopositivityof MPO was observed in neutrophil granulocytes within lung alveoli and lung blood vessels. Myeloperoxidase positivity was observed in alveolar macrophages, too. Vascular endothelial growth factor was expressed in cytoplasm of neutrophil granulocytes, monocytes, small-sized alveolar macrophages and type II pneumocytes localized mostly inside lung alveoli. On the contrary, no positivity was observed in lung endothelial cells of blood vessels.