• IMMUNE NETWORK
• /
• v.23 no.5
• /
• pp.42.1-42.21
• /
• 2023

When the lungs are infected with bacteria, alveolar macrophages (AMs) are recruited to the site and play a crucial role in protecting the host by reducing excessive lung inflammation. However, the regulatory mechanisms that trigger the recruitment of AMs to lung alveoli during an infection are still not fully understood. In this study, we identified a critical role for NADPH oxidase 4 (NOX4) in the recruitment of AMs during Staphylococcus aureus lung infection. We found that NOX4 knockout (KO) mice showed decreased recruitment of AMs and increased lung neutrophils and injury in response to S. aureus infection compared to wildtype (WT) mice. Interestingly, the burden of S. aureus in the lungs was not different between NOX4 KO and WT mice. Furthermore, we observed that depletion of AMs in WT mice during S. aureus infection increased the number of neutrophils and lung injury to a similar level as that observed in NOX4 KO mice. Additionally, we found that expression of intercellular adhesion molecule-1 (ICAM1) in NOX4 KO mice-derived lung endothelial cells was lower than that in WT mice-derived endothelial cells. Therefore, we conclude that NOX4 plays a crucial role in inducing the recruitment of AMs by controlling ICAM1 expression in lung endothelial cells, which is responsible for resolving lung inflammation during acute S. aureus infection.

• Radiation Oncology Journal
• /
• v.15 no.1
• /
• pp.37-47
• /
• 1997

Purpose : To investigate ultrastructural changes of the mouse lung induced by whole lung gamma irradiation and to evaluate the effect of prophylactic administration of steroid against acute lung injury. Materials and Methods :. One hundred and twenty ICR mice were used and whole lung was irradiated with telecobalt machine. Whole lung doses were 8 and 12Gy, and 10mg of methyl prednisolone was administrated intraperitoneally for two and four weeks. At the end of the observation period, mice were sacrificed by cervical dislocation. The lungs were removed and fixed inflated. Histopathological examination of acute radiation injuries were Performed by light microscopic and transmission electron microscopic examination. Results : Control group with BGy is characterized by damage to the type I Pneumocyte and the endothelial cell of the capillary. edema of alveolar wall and interstitium. and fibroblast proliferation. Control group with 120y is characterized by more severe degree of type 1 pneumocyte damage and more prominant inflammatory cell infiltration. Destructed cell debris within the alveolar space were also noted After steroid administration, 8Gy experimental group showed decreased degree of inflammatory reactions but fibroblast proliferation and basal lamina damages were unchanged. Experimental group with 12Gy showed lesser degree of inflammatory reactions similar to changes of 8Gy experimental group. Conclusion : These studies suggest that the degree of interstitial edema and inflammatory changes were related to radiation dose but Proliferation of the fibroblast and structural changes of basal lamina were not related to radialion dose. Experimental administration of steroid for 2 to 4 weeks after whole lung irradiation suggest that steroid can suppress alveolar and endothelial damages induced by whole lung irradiation but Proliferation of the fibroblast and structural changes of basal lamina were not related to administration of steroid.

• Tuberculosis and Respiratory Diseases
• /
• v.54 no.5
• /
• pp.532-541
• /
• 2003

Background : Phospholipase $A_2$ ($PLA_2$) has been known to be involved in the pathogenesis of acute lung injury (ALI) including ARDS. Since doxycycline has the property of inhibiting secretory group II $PLA_2$, the therapeutic effect of doxycycline hyclate was investigated for gut ischemia/reperfusion (I/R)-induced ALI in Sprague-Dawley rats. Methods : ALI was induced in Sprague-Dawley rats by clamping of the superior mesenteric artery for 60 min, followed by 120 min of reperfusion. To confirm the pathogenetic mechanisms of this ALI associated with neutrophilic oxidative stress, we measured bronchoalveolar lavage (BAL) protein content and lung MPO, and performed cyto-chemical electron microscopy for detection of free radicals, assay of $PLA_2$ activity and cytochrome-c reduction assay. Results : In gut I/R-induced ALI rats, protein leakage, pulmonary neutrophil accumulation, free radical production and lung $PLA_2$ activity were all increased. These effects were reversed by doxycycline hyclate. Conclusion : Doxycycline appears to be effective in ameliorating the gut I/R-induced ALI by inhibiting $PLA_2$, thereby decreasing the production of free radicals from neutrophils.

• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.2
• /
• pp.183-189
• /
• 2015

Foeniculum vulgare Mill. (fennel) is used to flavor food, in cosmetics, as an antioxidant, and to treat microbial, diabetic and common inflammation. No study to date, however, has assessed the anti-inflammatory effects of fennel in experimental models of inflammation. The aims of this study were to investigate the anti-inflammatory effects of fennel in model of lipopolysaccharide (LPS)-induced acute lung injury. Mice were randomly assigned to seven groups (n=7~10). In five groups, the mice were intraperitoneally injected with 1% Tween 80-saline (vehicle), fennel (125, 250, $500{\mu}l/kg$), or dexamethasone (1 mg/kg), followed 1 h later by intratracheal instillation of LPS (1.5 mg/kg). In two groups, the mice were intraperitoneally injected with vehicle or fennel ($250{\mu}l/kg$), followed 1 h later by intratracheal instillation of sterile saline. Mice were sacrificed 4 h later, and bronchoalveolar lavage fluid (BALF) and lung tissues were obtained. Fennel significantly and dose-dependently reduced LDH activity and immune cell numbers in LPS treated mice. In addition fennel effectively suppressed the LPS-induced increases in the production of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, with $500{\mu}l/kg$ fennel showing maximal reduction. Fennel also significantly and dose-dependently reduced the activity of the proinflammatory mediator matrix metalloproteinase 9 and the immune modulator nitric oxide (NO). Assessments of the involvement of the MAPK signaling pathway showed that fennel significantly decreased the LPS-induced phosphorylation of ERK. Fennel effectively blocked the inflammatory processes induced by LPS, by regulating pro-inflammatory cytokine production, transcription factors, and NO.

• Journal of Trauma and Injury
• /
• v.19 no.1
• /
• pp.14-20
• /
• 2006

Purpose: Although hypothermia has been used in many clinical situations, such as post cardiopulmonary resuscitation, stroke, traumatic brain injury, septic shock, and hemorrhagic shock, the mechanism by which it works has not been clearly elucidated. We aimed to evaluate the effect of hypothermia on the plasma nitric oxide (NO) concentration, lung iNOS expression, and histologic changes in intestinal ischemia-reperfusion (IR). Method: Male Sprague-Dawley rats were randomly divided into the hypothermia group (HT, n=8, $27{\sim}30^{\circ}C$) and the normothermia group (NT, n=8, $36{\sim}37^{\circ}C$). They underwent 30 min of intestinal ischemia by clamping the superior mesenteric artery, which was followed by 1.5 h of reperfusion. They were then sacrificed. The acute lung injury (ALI) score, the plasma NO concentration, and lung iNOS gene expression were measured. Results: Compared with the HT group, the NT group showed severe infiltrations of inflammatrory cells, alveolar hemorrhages, and interstitial hypertrophies in lung tissues. There were significant differences in the ALI scores between the NT and the HT groups ($8.7{\pm}1.5/HPF$ in NT vs $5.8{\pm}1.2/HPF$ in HT, p=0.008). Although the plasma NO concentration was slightly lower in the HT group, there was no significant difference between the two groups ($0.80{\pm}0.24{\mu}mol/L$ in NT vs $0.75{\pm}0.30{\mu}mol/L$ in HT, p=0.917). Lung iNOS gene expression was stronger in the NT group than in the HT group. The band density of the expression of iNOS in lung tissues was significantly increased in the NT group compared to the HT group ($5.54{\pm}2.75$ in NT vs$0.08{\pm}0.52$ in HT, p=0.002). Conclusions: This study showed that hypothermia in intestinal IR reduces inflammatory responses, ALI scores, and iNOS gene expression in lung tissues. There was no significant effect of hypothermia on the plasma NO concentration.

• The Journal of Internal Korean Medicine
• /
• v.11 no.2
• /
• pp.1-15
• /
• 1990

Certain oriental medication have been shown to be effective in decreasing pulmonary vascular resistance and increasing cardiac output in primary pulmonary artery pressure secondary to pulmonary edema. So oleic acid was administered in 14 dogs in order to induce acute lung injury. And we studied the hemodynamics and blood gas changes of Pyengpaetang(50mg, 100mg) with continuous postive pressure was ventilation in pulmonary edema. The pulmonary edema group, arterial oxygenation was improved after 5 and $10cmH_2O$ PEEP(positive end expiratory pressure), but cardiovascular system was depressed. Blood pressure and cardiac output were decreased, and CVP, MP AP, PCWP were increased. In Pyengpaetang(50mg) group, mean aortic pressure was decreased and PCWP(pulmonary capillary wedge pressure) was decreased remarkably, while there was a significant increase in cardiac output. And there was improvement in $PaO_2$ and $PaCO_2$ without hemodynamic changes after applying 5cm $H_2O$ PEEP, but arterial blood gases$(PaO_2,\;PaCO_2)$ were improved, while cardiovascular effects were depressed after cm $H_2O$ PEEP. In Pyengpaetang(100mg) treated group, there was no significant hemodynamic change. But mean pulmonary arterial pressure was significantly increased, and cardiac output was decreased significantly after applying the more degree of PEEP. And blood gases were not changed significantly after applying the more degree of PEEP. The above results suggest that the effects of Pyengpaetang(50mg) group is superior to those of Pyengpaetang(100mg) group on the effects of hemodynamics and gas exchanges in acute lung injury in dogs. So we can conclude that lower degree PEEP 5cm $H_2O$ is more beneficial in Pyengpaetang(50mg) treated group.

• Clinical and Experimental Pediatrics
• /
• v.63 no.7
• /
• pp.239-250
• /
• 2020

The novel coronavirus disease 2019 (COVID-19) is spreading globally. Although its etiologic agent is discovered as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), there are many unsolved issues in COVID-19 and other infectious diseases. The causes of different clinical phenotypes and incubation periods among individuals, species specificity, and cytokine storm with lymphopenia as well as the mechanism of damage to organ cells are unknown. It has been suggested that in viral pneumonia, virus itself is not a direct cause of acute lung injury; rather, aberrant immune reactions of the host to the insults from viral infection are responsible. According to its epidemiological and clinical characteristics, SARS-CoV-2 may be a virus with low virulence in nature that has adapted to the human species. Current immunological concepts have limited ability to explain such unsolved issues, and a presumed immunopathogenesis of COVID-19 is presented under the protein-homeostasis-system hypothesis. Every disease, including COVID-19, has etiological substances controlled by the host immune system according to size and biochemical properties. Patients with severe pneumonia caused by SARS-CoV-2 show more severe hypercytokinemia with corresponding lymphocytopenia than patients with mild pneumonia; thus, early immunomodulator treatment, including corticosteroids, has been considered. However, current guidelines recommend their use only for patients with advanced pneumonia or acute respiratory distress syndrome. Since the immunopathogenesis of pneumonia may be the same for all patients regardless of age or severity and the critical immune-mediated lung injury may begin in the early stage of the disease, early immunomodulator treatment, including corticosteroids and intravenous immunoglobulin, can help reduce morbidity and possibly mortality rates of older patients with underlying conditions.

• Tuberculosis and Respiratory Diseases
• /
• v.60 no.5
• /
• pp.564-570
• /
• 2006

Toxic gases and soot deposition as a consequence of smoke inhalation can cause direct injury to the upper and lower airways and even to the lung parenchyma. A delay in proper and prompt therapy can be detrimental to critically ill burn patients with an inhalation injury. Therefore, serial chest radiography is an important diagnostic tool for pulmonary complications during treatment. The radiographic findings of the chest include normal, consolidation, interstitial and alveolar infiltrates, peribronchial thickening, atelectasis, cardiogenic and non-cardiogenic pulmonary edema, and a pneumothorax as acute complications of smoke inhalation. In addition, bronchiectasis, bronchiolitis obliterans and pulmonary fibrosis can occur as late complications. We encountered a case of 44-year-old male who presented with acute lung injury after an inhalation injury. He required endotracheal intubation and mechanical ventilation due to respiratory failure. He was managed successfully with conservative treatment. Later, a cavitary lesion of the left upper lobe was observed on the chest radiography and computed tomography, which was complicated by massive hemoptysis during the follow-up. However, the cavitary lesion disappeared spontaneously without any clinical consequences.

• Tuberculosis and Respiratory Diseases
• /
• v.60 no.4
• /
• pp.437-450
• /
• 2006

Background : Acute respiratory distress syndrome (ARDS) is characterized by severe inflammatory pulmonary edema of unknown pathogenesis. To investigate the pathogenesis of ARDS associated with neutrophilic oxidative stress, the role of phospholipase $A_2$ ($PLA_2$) was evaluated by the inhibition of calcium channel. Methods : In Sprague-Dawley rats, acute lung injury (ALI) was induced by the instillation of E.coli endotoxin (ETX) into the trachea. At the same time, diltiazem was given 60 min prior to tracheal instillation of ETX. Parameters of ALI such as lung and neutrophil $PLA_2$, lung myeloperoxidase (MPO), BAL neutrophils, protein, surfactant were measured. Production of free radicals from neutrophils was measured also. Morphological studies with light microscope and electron microscope were carried out and electron microscopic cytochemistry for detection of free radicals was performed also. Results : Diltiazem had decreased the ALI parameters effectively in ETX given rats and decreased the production of free radicals from neutrophils and lung tissues. Morphological studies denoted the protective effects of diltiazem. Conclusion : Diltiazem, a calcium channel blocker, was effective in amelioration of ALI by the suppression of neutrophilic oxidative stress mediated by $PLA_2$ activation.

• Tuberculosis and Respiratory Diseases
• /
• v.51 no.2
• /
• pp.161-165
• /
• 2001

Acute bilateral reexpansion pulmonary edema after pleurocentesis is a rare complication. In one case, bilateral reexpansion pulmonary edema after unilateral pleurocentensis in sarcoma was reported. Various hypotheses regarding the mechanism of reexpansion pulmonary edema include increased capillary permeability due to hypoxic injury, decreased surfactant production, altered pulmonary perfusion and mechanical stretching of the membranes. Ragozzino et al suggested that the mechanism leading to unilateral reexpansion pulmonary edema involves the opposite lung when there is significant contralateral lung compression. Here we report a case of bilateral reexpansion pulmonary edema and acute respiratory distress syndrome after a unilateral pleurocentesis of a large pleural effusion with contralateral lung compression and increased interstitial lung marking underlying chronic liver disease.