Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476273 (respiratory distress)
 19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhaled endotoxin (lipopolysaccharide, LPS) can induce acute lung injury and at high doses may lead to respiratory distress syndrome. Using a mouse model of acute lung inflammation induced by inhalation of low doses of LPS we examined the kinetics of chemokine, proinflammatory cytokine, and metallothionein. Eight-week-old C57BL/6 mice were dosed for 10 min with LPS, resulting in an estimated alveolar dose of < 10 ng LPS/mouse, and euthanized 2,6, or 24 h postexposure. Analysis of bronchoalveolar lavage fluid demonstrated increased polymorphonuclear neutrophils (PMNs) of 6.94, 32.7, and 38.8% after 2, 6, and 24 h, respectively. Examination of proinflammatory cytokine, chemokine, and Mt mRNA in the lung revealed increases for messages encoding IL-1 alpha, IL-1 beta, IL-6, IFN-gamma, TNF alpha, Eotaxin, MIP-1 alpha, MIP-1 beta, MIP-2, Mt, and IP-10, while messages encoding IL-12, IL-10, IFN-beta, Ltn, MCP-1, TGF beta 1 + 2, and RANTES were unchanged from those of sham-exposed mice 2 h postexposure. By 6 h most messages had returned to near control levels. Comparison to 5 mg/kg body weight intraperitoneal injection and 5 micrograms/mouse intratracheal instillation 2 h postexposure demonstrated similar message responses. Our results demonstrate that low levels of LPS exposure by inhalation induce a strong PMN response and a selective cytokine response in the lung, supporting the hypothesis that PMNs may regulate inflammatory processes via cytokine and chemokine response.
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PMID:Pulmonary cytokine and chemokine mRNA levels after inhalation of lipopolysaccharide in C57BL/6 mice. 1004 33

In 49 acute respiratory distress syndrome (ARDS) patients, the phenotype of alveolar macrophages (AMs) was analyzed by flow cytometry. Bronchoalveolar lavage (BAL) was performed within 24 h after intubation and on days 3-5, 9-12, and 18-21 of mechanical ventilation. The 27E10(high)/CD11b(high)/CD71(low)/ 25F9(low)/HLA DR(low)/RM3/1(low) AM population in the first BAL indicated extensive monocyte influx into the alveolar compartment. There was no evidence of increased local AM proliferation as assessed by nuclear Ki67 staining. Sequential BAL revealed two distinct patient groups. In one, a decrease in 27E10 and CD11b and an increase in CD71, 25F9, HLA DR, and RM3/1 suggested a reduction in monocyte influx and maturation of recruited cells into AMs, whereas the second group displayed sustained monocyte recruitment. In the first BAL from all patients, monocyte chemoattractant protein (MCP)-1 was increased, and AMs displayed elevated MCP-1 gene expression. In sequential BALs, a decrease in MCP-1 coincided with the disappearance of monocyte-like AMs, whereas persistent upregulation of MCP-1 paralleled ongoing monocyte influx. A highly significant correlation between BAL fluid MCP-1 concentration, the predominance of monocyte-like AMs, and the severity of respiratory failure was noted.
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PMID:Phenotypic characterization of alveolar monocyte recruitment in acute respiratory distress syndrome. 1089 99

Endotoxin-induced microvascular lung injury in mice is a commonly used experimental model of the acute respiratory distress syndrome (ARDS). The present paper aimed to characterize this popular model in a comprehensive and systematic fashion. Male C57bl/6 mice (n = 5) were administered an LD55 dose of E. coli endotoxin (15 mg/kg, i.p.), and lungs were harvested at several time points and evaluated for injury as well as for expression of a variety of inflammatory mediators. Endotoxin induced many features characteristic of acute microvascular lung injury. These included early (1-2 h) expression of inflammatory mediators (IL-1alpha, IL-1beta, IL-4, IL-6, IL-10, TNF-alpha, interferon-alpha, interferon gamma, and MCP-1) and leukocyte accumulation in lung tissue (lung myeloperoxidase activity 18.5 +/- 7.8 U/g tissue, P < 0.05), followed by pulmonary edema (lung water content index 17.4% +/- 2.5%, P < 0.05) and mortality. Histopathological evaluation of lung tissue was compatible with these findings. The characterization of this murine model of endotoxin-induced microvascular injury will facilitate its utilization in ARDS research.
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PMID:Characterization of a murine model of endotoxin-induced acute lung injury. 1195 30

Mounting evidence suggests that CCL2 (MCP-1) and its hematopoietic cell receptor CC chemokine receptor 2 (CCR2) are involved in inflammatory disorders of the lung. In animal models of allergic asthma, idiopathic pulmonary fibrosis (IPF), and bronchiolitis obliterans syndrome (BOS), CCL2 expression and protein production are increased and the disease process is attenuated by CCL2 immunoneutralization. Mechanisms by which CCL2 may be acting include recruitment of regulatory and effector leukocytes; stimulation of histamine or leukotriene release from mast cells or basophils; induction of fibroblast production of transforming growth factor-beta (TGF-beta) and procollagen; and enhancement of Th2 polarization. Recently, polymorphism for CCL2 has been described with increased cytokine-induced release of CCL2 by monocytes and increased risk of allergic asthma. These studies identify potentially important roles for CCL2 in these lung inflammatory disorders. While CCL2 inhibition in patients with acute respiratory distress syndrome (ARDS) may be hazardous by interfering with defense against bacteremia, future studies are needed to determine if CCL2/CCR2 antagonism will offer breakthrough therapy for patients with allergic asthma, IPF, or BOS, and to confirm the hypothesis that CCL2 polymorphism places patients at greater risk for these disorders.
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PMID:Significant involvement of CCL2 (MCP-1) in inflammatory disorders of the lung. 1285 45

Inflammation is one of the primary processes underlying respiratory distress syndrome (RDS) and its evolution into bronchopulmonary dysplasia (BPD). Recruitment and subsequent activation of macrophages in the lung are mediated by CC chemokines. The role of CC chemokines has not been extensively studied in the course of RDS. Serial tracheal aspirates (TA) were obtained from 56 mechanically ventilated infants with birth weights less than 1,500 g during intervals in the first 21 days of life. Tracheal aspirate concentrations of monocyte chemoattractant proteins-1,2,3 (MCP-1,2,3) and macrophage inflammatory proteins-1alpha and -1beta (MIP-1alpha, MIP-1beta) were determined by enzyme-linked immunosorbent assay (ELISA). Tracheal aspirate concentrations of MCP-1, MCP-2, MCP-3, and MIP-1beta increased during the first week of life in infants with RDS, whereas MIP-1alpha concentrations did not increase appreciably. Increased TA cytokine concentrations were associated with the development of BPD. Maximal TA concentrations of MCP-1, MCP-2, MCP-3, MIP-1alpha, and MIP-1beta were significantly higher in infants who were oxygen-dependent at 28 postnatal days compared to infant who were not. Similarly, maximal TA MCP-1, MCP-2, and MCP-3 but not MIP-1alpha and MIP-1beta concentrations were significantly higher in infants who were oxygen-dependent at 36 weeks of postconceptional age (PCA) than those who were not oxygen-dependent at 36 weeks PCA. Histologic chorioamnionitis and isolation of Ureaplasma urealyticum from the airways were associated with higher maximal TA concentrations of MIP-1alpha and MIP-1beta. Pulmonary hemorrhage was associated with increased maximal concentrations of MCP-1, MCP-2, and MCP-3. These data suggest a role for CC chemokines in the development of BPD in the newborn infant.
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PMID:CC chemokine concentrations increase in respiratory distress syndrome and correlate with development of bronchopulmonary dysplasia. 1473 Jun 59

Impact of blast shock waves (SW) with the body wall produces blast lung injuries characterized by bilateral traumatic hemorrhages. Such injuries often have no external signs, are difficult to diagnose, and therefore, are frequently underestimated. Predictive assessment of acute respiratory distress syndrome outcome in SW-related accidents should be based on experimental data from appropriate animal models. Blood plasma transferrin is a major carrier of blood iron essential for proliferative "emergency" response of hematopoietic and immune systems as well as injured tissue in major trauma. Iron-transferrin complexes (Fe3+ TRF) can be quantitatively analyzed in blood and tissue samples with low-temperature EPR techniques. We hypothesized that use of EPR techniques in combination with assays for pro-inflammatory cytokines and granulocytes in the peripheral blood and BAL would reveal a pattern of systemic sequestration of (Fe3+)TRF that could be useful for development of biomarkers of the systemic inflammatory response to lung injury. With this goal we (i) analyzed time-dependent dynamics of (Fe3+)TRF in the peripheral blood of rats after impacts of SW generated in a laboratory shock-tube and (ii) assayed the fluctuation of granulocyte (PMN) counts and expression of CD11b adhesion molecules on the surface of PMNs during the first 24 h after SW induced injury. Sham-treated animals were used as control. Exposure to SW led to a significant decrease in the amount of blood (Fe3+)TRF that correlated with the extent of lung injury and developed gradually during the first 24 h. Thus, sequestration of (Fe3+)TRF occurred as early as 3 h post-exposure. At that time, the steady state concentration of (Fe3+)TRF in blood samples decreased from 19.7+/-0.6 microM in controls to 7.5+/-1.3 microM in exposed animals. The levels of (Fe3+)TRF remained decreased throughout the entire study period. PMN counts increased 5-fold and 3.5-fold over controls respectively, at 3 and 6 h postexposure. These effects were accompanied by an increase in expression of CD11b on the surface membrane of PMNs. Extensive release of cytokines IL-1, IL-6, MCP-1, and MIP-2 was observed in BAL fluid and blood plasma during 24 h postexposure. We conclude that EPR monitoring of blood (Fe3+)TRF can be a useful approach for assessment of systemic pro-inflammatory alterations due to SW-induced lung injury.
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PMID:Pro-inflammatory alterations and status of blood plasma iron in a model of blast-induced lung trauma. 1616 36

We investigated the effects of Xia-Bai-San (XBS) on acute lung inflammation induced by LPS in vivo. Mice were challenged with intratracheal lipopolysaccharide (100 microg) 30 min before administering XBS (1 mg/kg oral administration). Bronchoalveolar lavage fluid (BALF) was obtained after 4 and 24 h to measure proinflammatory cytokine (TNF-alpha, IL-1beta, IL-6), anti-inflammatory cytokines (IL-10), chemokines (KC, MCP-1 and MIP-2), total cell counts, nitric oxide production, and proteins. The results indicated that XBS down-regulated the LPS-induced expression of TNF-alpha, IL-1beta, IL-6, KC, MIP-2, and MCP-1. Furthermore, it also enhanced the production of IL-10, which had increased 24 h after LPS challenge. In addition, total leukocyte counts, nitric oxide production, iNOS expression, and BALF's proteins had significantly decreased 24 h after LPS challenge. XBS was also believes to have reduced the acute inflammation by attenuating the activation of NF-kappaB. In conclusion, XBS seem to suppress lipopolysaccharide-induced lung inflammation by stimulating the production of anti-inflammatory cytokines in lung. These results suggest that XBS could be a useful adjunct in the treatment of acute respiratory distress syndrome.
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PMID:Protective and anti-inflammatory effect of a traditional Chinese medicine, Xia-Bai-San, by modulating lung local cytokine in a murine model of acute lung injury. 1684 45

Severe acute respiratory syndrome (SARS) presented as an atypical pneumonia that progressed to acute respiratory distress syndrome in approximately 20% of cases and was associated with a mortality of about 10%. The etiological agent was a novel coronavirus (CoV). Angiotensin-converting enzyme 2 is the functional receptor for SARS-CoV; DC-SIGN and CD209L (L-SIGN) can enhance viral entry. Although the virus infects the lungs, gastrointestinal tract, liver, and kidneys, the disease is limited to the lungs, where diffuse alveolar damage is accompanied by a disproportionately sparse inflammatory infiltrate. Pro-inflammatory cytokines and chemokines, particularly IP-10, IL-8, and MCP-1, are elevated in the lungs and peripheral blood, but there is an unusual lack of an antiviral interferon (IFN) response. The virus is susceptible to exogenous type I IFN but suppresses the induction of IFN. Innate immunity is important for viral clearance in the mouse model. Virus-specific neutralizing antibodies that develop during convalescence prevent reinfection in animal models.
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PMID:The Immunobiology of SARS*. 1724 93

All-trans retinoic acid (ATRA) can induce acute respiratory distress syndrome in patients with acute promyelocytic leukaemia (APL). The current study investigated the role of monocyte chemotactic protein (MCP)-1 in the chemotactic transmigration of ATRA-treated NB4 (ATRA-NB4) APL cells toward A549 alveolar epithelial cells. NB4 and A549 cells were separately cultured with ATRA and/or dexamethasone (DEX). ATRA-NB4 cells were then placed in an upper insert and co-incubated with A549 cells or their conditioned medium (CM) located in a lower plate to test their transmigration activity. ATRA stimulated NB4 cells to transmigrate toward the A549 cells. The secretion of MCP-1 was enhanced by ATRA treatment in both A549 and NB4 cells. The binding assay demonstrated that ATRA-NB4 cells bound MCP-1. Pre-treatment of both CM-A549 cells with antibodies against MCP-1 and of ATRA-NB4 cells with antibodies against MCP-1 receptors reduced ATRA-NB4 cell transmigration. DEX did not suppress MCP-1 secretion and transmigration in ATRA-NB4 cells, although when applied to A549 cells, MCP-1 secretion was suppressed and ATRA-NB4 cell transmigration was attenuated. Monocyte chemotactic protein-1 secreted from alveolar epithelial cells plays an important role in the cell-cell interaction involved in the chemotactic transmigration of all-trans retinoic acid-treated acute promyelocytic leukaemia cells toward alveolar epithelial cells.
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PMID:Monocyte chemotactic protein-1 in the migration of differentiated leukaemic cells toward alveolar epithelial cells. 1821 48

Increased levels of interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 have been found in bronchoalveolar lavage fluid of acute respiratory distress syndrome (ARDS) patients. The authors investigated whether inflammatory-activated microvascular pulmonary endothelial cells (HMVECL) regulate expression of IL-8 and MCP-1 in the alveolar epithelial cell line A549 and studied the effects of hypoxia (5% O(2)) and hyperoxia (85% O(2)). The authors observed significant up-regulation of IL-8 and MCP-1 expression in A549 cells that was independent from the IL-1 receptor pathway but was modified by oxygen tension. These data show that the pulmonary microvascular endothelium is able to regulate epithelial cell chemokine expression in a paracrine fashion.
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PMID:Inflammatory-activated microvascular endothelial cells regulate interleukin-8 and monocyte chemoattractant protein-1 expression of A549 cells in a paracrine fashion. 1826 31


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