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At least 127 records · Page 7Linked to original sources
PubMed2006

Reversal of airway inflammation and remodeling in asthma by a bispecific antibody fragment linking CCR3 to CD300a.

BACKGROUND: Mast cells (MCs) and eosinophils are critically involved in asthma-associated airway damage and remodeling. However, molecular pathways that inhibit their functions in this process have been scarcely characterized. Recently we established that cross-linking of CD300a inhibits MC and eosinophil activation. OBJECTIVE: To inhibit effector cell functions in a chronic model of experimental asthma by coaggregation of CD300a with CC chemokine receptor 3 (CCR3) using a bispecific antibody fragment (LC1). METHODS: Mast cells and eosinophils were treated with LC1 before their activation. Mediator release, survival, and intracellular signaling were assessed. Furthermore, chronic experimental asthma was induced, and starting on day 30, the mice were challenged (3 challenges/wk) for an additional 38 days. With each challenge, the mice received LC1 intranasally. RESULTS: LC1 inhibited MCs and eosinophil activation in vitro and in vivo. Mice that displayed airway inflammation on day 28 and were treated with LC1 completely recovered from the disease process. In the bronchoalveolar lavage fluid of these mice, cellular inflammation cytokine expression was comparable to that of saline-treated mice. Bronchoalveolar lavage fluid levels of TGF-beta1 correlated significantly with reduced eosinophilia. Histologic analysis revealed significant reduction in lung inflammation, mucus production, collagen deposition, and peribronchial smooth-muscle thickening. CONCLUSION: CD300a is a critical modulator of MCs and eosinophil functions in allergic settings. CLINICAL IMPLICATIONS: Specific targeting of CD300a in CCR3(+) cells may be a potent tool for treating airway inflammation and tissue remodeling in asthma.

Administration, Intranasal↗
PubMed2003

Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability.

Inflammation plays a central pathogenic role in the initiation and progression of coronary atheroma and its clinical consequences. Cytokines are the mediators of cellular inflammation and promote local inflammation in the arterial wall, which may lead to vascular smooth muscle apoptosis, degradation of the fibrin cap and plaque rupture. Platelet adhesion and thrombus formation then occur, resulting clinically in unstable angina or myocardial infarction. Recent studies have suggested that cytokines are pathogenic, contributing directly to the disease process. 'Anti-cytokine' therapy may, therefore, be of benefit in preventing or slowing the progression of cardiovascular disease. Both oestrogens and testosterone have been shown to have immune-modulating effects; testosterone in particular appears to suppress activation of pro-inflammatory cytokines. Men with low testosterone levels are at increased risk of coronary artery disease. An anti-inflammatory effect of normal physiological levels of sex hormones may, therefore, be important in atheroprotection. In this Article, we discuss some of the mechanisms involved in atherosclerotic coronary artery disease and the putative link between testosterone deficiency and atheroma formation. We present the hypothesis that the immune-modulating properties of testosterone may be important in inhibiting atheroma formation and progression to acute coronary syndrome.

Apoptosis↗
PubMed2004

Erythropoietin in the brain: can the promise to protect be fulfilled?

Erythropoietin (EPO) has emerged as a versatile growth factor that has transcended its traditional role as a mediator of erythroid maturation to one that modulates stem cell development, cellular protection and angiogenesis in the brain. As a possible candidate for nervous system disorders, it becomes crucial to understand the cellular mechanisms that foster cytoprotection rather than cytotoxicity for EPO. EPO offers novel neuronal and vascular protection not only through the maintenance of cellular integrity, but also through the prevention of cellular inflammation. The protective and anti-inflammatory capacities of EPO originate with the Janus tyrosine kinase 2 protein and protein kinase B (Akt). Downstream cellular pathways include FOXO3a, GSK-3beta, Bad, Bcl-xL, NF-kappaB, mitochondrial membrane permeability, APAF-1 and caspases. Further understanding of the cellular pathways that are susceptible to modulation by EPO will be crucial to foster the development of this agent as a robust and efficacious therapy for the brain.

Apoptosis↗
PubMedDate not supplied

Small bowel of patients with asthma and allergic rhinitis: absence of inflammation despite the presence of major cellular components of allergic inflammation.

Eosinophils participate in the pathogenesis of inflammatory diseases of the respiratory tract and the gut. We investigated the constitutive presence of eosinophils and mononuclear cells in the macroscopically normal duodenal mucosa of patients with asthma and allergic rhinitis. Macroscopically normal duodenal specimens were obtained at routine endoscopy for upper gastrointestinal symptoms from 16 patients with asthma and 13 patients with allergic rhinitis. Twelve nonatopic patients with irritable bowel syndrome were studied as controls. Specimens were analyzed by immunohistochemistry using a panel of antibodies to human eosinophil cationic protein clone EG1 (EG1) and clone EG2 (EG2), anti-human interleukin (anti-hIL)-5, anti-hIL-4, anti-CD4, and anti-CD68. Significantly increased numbers of eosinophils stained with EG1 and EG2 were found in the duodenum of patients with asthma and allergic rhinitis compared with controls. IL-5+ cells and IL-4+ cells were detected in significantly increased numbers in the duodenal mucosa of patients with asthma and rhinitis compared with controls. Mononuclear cells expressing CD4 (helper T cells) and CD68 (macrophages) also were significantly increased in the duodenal mucosa of asthma and rhinitis compared with controls. Accumulation of eosinophils in conjunction with IL-4+ cells and IL-5+ cells in the noninflamed duodenal mucosa may reflect a predominant T helper cell subset 2 systemic immune response in patients with asthma and allergic rhinitis. The absence of intestinal inflammation despite the marked presence of cells implicated in the allergic inflammation suggests that local mechanisms might determine the state of nonresponsiveness in the gut mucosa of patients with asthma and allergic rhinitis.

Adult↗
PubMed1997

Obliterative airway disease after heterotopic tracheal xenotransplantation: pathogenesis and prevention using new immunosuppressive agents.

BACKGROUND: The purpose of this study was to investigate whether obliterative bronchiolitis might occur after xenogenic pulmonary transplantation. A model for obliterative airway disease (OAD) after tracheal allograft transplantation in the rat undergoes tracheal obliteration with histologic features characteristic of obliterative bronchiolitis in human lung transplant recipients. Using this model, the pathogenesis of OAD and its prevention with immunosuppressive drugs was studied in rat recipients of hamster tracheal grafts. METHODS: Tracheae from 30 hamsters (xenografts) or 23 Brown-Norway rats (allografts) were implanted and wrapped in the greater omentum of untreated Lewis rats. The grafts were removed on day 1, 3, 7, 14, 21, or 28 after transplantation and stained with hematoxylin and eosin and Masson's trichrome and by immunohistochemistry and immunofluorescence (IFL) techniques. In addition, 25 recipients were treated with cyclosporine (CsA, 10 mg/kg p.o.), leflunomide (LFM, 20 mg/kg p.o.), or rapamycin (RPM, 6 mg/kg i.p.) for 14 or 21 days (5 animals per treatment group). Visual and morphometric analyses were used to evaluate the extent of airway obliteration, luminal coverage by respiratory or flattened cuboidal epithelium, and extent and density of peritracheal cellular inflammation. RESULTS: In all xenografts, a neutrophilic infiltration of the mucosa and submucosa was observed from day 1 until day 14 and was associated with complete loss of tracheal epithelium by day 14. A marked peritracheal mononuclear cellular infiltrate mixed with plasma cells and eosinophils was seen on days 7 and 14. Both the extent of peritracheal inflammation and the density of the mononuclear cell infiltrate were significantly increased in xenograft tracheae when compared with the allografts. Tracheal obliteration began on day 14 and reached a maximum of 43% on day 21 with evidence of intraluminal fibrosis. In contrast to IFL of allografts, IFL of xenografts demonstrated marked deposition of rat immunoglobulin in the peritracheal tissue on days 7 and 14. The effects of treatment with immunosuppressive drugs on tracheal graft narrowing and protection of respiratory epithelium were as follows: After 14 days of treatment, the percentage of tracheal graft narrowing was 12%, 23%, and 19% in the no treatment, CsA, and LFM groups, respectively; the percentage of respiratory epithelium at 14 days was 0%, 21%, and 95%. After 21 days of treatment, the percentage of tracheal graft narrowing was 43%, 49%, 12%, and 5% for the no treatment, CsA, LFM, and RPM groups, respectively; the percentage of respiratory epithelium at 21 days was 0%, 39%, 86%, and 0%. Using computerized morphometry, the extent and densities of the peritracheal cellular infiltrates were significantly reduced in LFM- and CsA-treated groups when compared with untreated xenograft controls. LFM and RPM, but not CsA, significantly reduced the degree of luminal obliteration compared with no treatment (P<0.05). LFM and, to a lesser extent, CsA were able to prevent the loss of normal respiratory epithelium. Analysis by IFL revealed a marked decrease in rat immunoglobulin deposition in xenografts from LFM- and RPM-treated groups compared with xenografts from CsA-treated or untreated rats. CONCLUSIONS: (1) OAD occurs not only after tracheal allotransplantation but also after xenotransplantation. (2) Subepithelial infiltration of neutrophils and the appearance of plasma cells and eosinophils in the peritracheal infiltrates distinguished the histology of rejected xenografts from allografts. (3) Antibody deposition was detected by IFL only in xenografts. (4) Treatment with LFM or RPM significantly decreased the severity of luminal obliteration. Importantly, LFM also prevented the loss of respiratory epithelium.

Airway Obstruction↗
PubMed2006

Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner.

Serum amyloid A (SAA) is an amphiphilic helical protein that is found associated with plasma HDL in various pathological conditions, such as acute or chronic inflammation. Cellular lipid release and generation of HDL by this protein were investigated, in comparison with the reactions by apolipoprotein A-I (apoA-I) and several types of cells that appear with various specific profiles of cholesterol and phospholipid release. SAA mediated cellular lipid release from these cells with the same profile as apoA-I. Upregulation of cellular ABCA1 protein by liver X receptor/retinoid X receptor agonists resulted in an increase of cellular lipid release by apoA-I and SAA. SAA reacted with the HEK293-derived clones that stably express human ABCA1 (293/2c) or ABCA7 (293/6c) to generate cholesterol-containing HDL in a similar manner to apoA-I. Dibutyryl cyclic AMP and phorbol 12-myristate 13-acetate, which differentiate apoA-I-mediated cellular lipid release between 293/2c and 293/6c, also exhibited the same differential effects on the SAA-mediated reactions. No evidence was found for the ABCA1/ABCA7-independent lipid release by SAA. Characterization of physicochemical properties of the HDL revealed that SAA-generated HDL particles had higher density, larger diameter, and slower electrophoretic mobility than those generated by apoA-I. These results demonstrate that SAA generates cholesterol-containing HDL directly with cellular lipid and that the reaction is mediated by ABCA1 and ABCA7.

ATP Binding Cassette Transporter 1↗
PubMed2006

Diffuse mucosal inflammation in nasal polyps and adjacent middle turbinate.

BACKGROUND: Nasal polyp (NP) is the most common mass lesion in the nose with unclear etiology and pathogenesis. OBJECTIVE: To investigate the association of allergy and type of cellular inflammation in Asian patients with NPs. METHODS: Immunohistochemical staining with a panel of antibodies for CD4+ and CD8+ T cells, B cells, Langerhans' cells, eosinophils, neutrophils, and mast cells were performed in pairs of NP tissue and middle turbinate (MT) biopsies from the same side of 48 patients and MT of controls. Serum total IgE and specific IgE to a panel of common local allergens were tested by the UniCAP (Pharmacia & Upjohn AB, Uppsala, Sweden) system. RESULTS: Atopy was found in 29.7% of NP patients. Strong correlations of cell scores were evidenced between the paired samples from nasal polyp patients. The cell patterns in nasal polyp mainly showed a combined cell infiltration with significantly higher CD8+ T cell, eosinophil and neutrophil scores, and an inverse median ratio of CD4+/CD8+ T cells as compared with the MT from controls. CONCLUSION: The similar immunohistochemical pattern of mucosal inflammation in NPs and the paired MT mucosa suggests a diffuse mucosal involvement. This indicates the necessity of anti-inflammatory treatment of changes in the adjacent nasal mucosa in addition to the surgical removal of NPs. Besides the well-recognized eosinophilic inflammation in Caucasian studies, predominant infiltration of T cells, especially CD8+ T cells, could be a key component underlying the pathogeneses of NPs.

Adolescent↗
PubMed1998

Cytokine mediation of ozone-induced pulmonary adaptation.

Previous studies have shown that a single exposure of animals to ozone (O3) can induce protection or adaptation to the acute injurious effects of a subsequent O3 challenge. Although a number of mechanisms have been proposed to account for this response, none appear to be fully explanatory. We examined the role interleukin (IL)-6 may play in the induction of adaptation to O3-induced pulmonary injury. A statistically significant 29-fold increase in bronchoalveolar lavage fluid IL-6 levels was observed in rats exposed to 0.5 ppm O3 during nighttime hours when compared with daytime hours even though similar kinetics of inflammation were induced by each exposure. Animals receiving an initial nighttime O3 exposure showed a lesser degree of inflammation following a subsequent O3 exposure when compared with animals which received an initial daytime exposure. Rats pretreated with IL-6 both intratracheally and intraperitoneally and subsequently exposed to O3 showed a lesser degree of cellular inflammation when compared with respective controls. Pretreatment of rats with anti-IL-6-receptor antibodies (ra) prior to the nighttime O3 exposure completely abrogated the O3-induced cellular adaptive response without effecting the inflammatory response induced by the initial nighttime O3 exposure. In fact, administration of anti-IL-6ra augmented the neutrophil influx following the second O3 exposure. Anti-IL-6ra treatment did not alter the pulmonary edema adaptive response, suggesting that the O3-induced cellular and edema adaptive responses are regulated by different mechanisms. Our data indicate that mobilization of pulmonary antioxidants does not play a role in the IL-6-mediated early cellular adaptive response and suggest that IL-6 is an essential mediator of the O3-induced cellular adaptive response.

Adaptation, Physiological↗
PubMed1987

Dietary influences of evening primrose and fish oil on the skin of essential fatty acid-deficient guinea pigs.

There have been reports that certain dietary lipids are capable of regulating cellular inflammation and hyperproliferation. To investigate further the role of dietary manipulation involving gamma-linolenic acid (18:3n-6) and eicosapentaenoic acid (20:5n-3) on hyperproliferative cellular components, the effects of orally administered primrose oil (containing 18:3n-6) and menhaden fish oil (containing 20:5n-3) were tested in a cutaneous system using the essential fatty acid (EFA)-deficient guinea pig fed a hydrogenated coconut oil (HCO) diet. The effects of the dietary crossover regimen were determined on epidermal 1) morphology, 2) DNA synthesis, 3) delta 6- and delta 5-desaturase activities and 4) fatty acid composition of skin and liver lipids. Our results demonstrated that dietary fish oil lacked the capacity to reverse the signs of epidermal hyperproliferation, acanthosis and hypergranulosis that are characteristic of EFA deficiency. In contrast, primrose oil feeding reversed the histological and biochemical signs of hyperproliferation. These results suggest that dietary fish oil, which contains largely the 20:5n-3 fatty acid, lacks EFA-functional properties in the skin. In addition, substitution of HCO with primrose or fish oil after 6 wk revealed incorporation of 18:3n-6 and 20:5n-3 into epidermal lipids, respectively. The significance of these altered epidermal fatty acid profiles is discussed.

Animals↗
PubMed1989

Spontaneous disseminated panarteritis in laboratory beagle dogs in a toxicity study: a possible genetic predilection.

Disseminated panarteritis was found in 16 (9 males and 7 females) of 49 laboratory beagle dogs (25 males and 24 females) from one breeding kennel. The dogs had been used in a 6-month oral toxicity study. Panarteritis was not associated with clinical or gross abnormalities. The incidence was similar in the control and test article-treated groups. Mainly medium-sized arteries throughout the body, particularly intercostal arteries (at their aortic origin), and coronary, epididymal and thymic vessels were affected. Chronic mononuclear-cell periarteritis was the predominant feature. Mixed cellular inflammation of the wall, proliferation or degeneration of muscle cells, focal "fibrinoid" material in the tunica media, fragmented internal elastic lamina and intimal thickening associated with myointimal cellular proliferation also occurred. These histologic changes are compatible with those of immune arteritis. Round worm intestinal infestation and granulomas of visceral larva migrans were common in several organs. Statistical analyses suggested that the pedigree of dogs is related to panarteritis, but the presence or absence of parasitization alone is not. The possible roles of genetic predilection and/or parasites in the pathogenesis are discussed. This panarteritis is spontaneous and may complicate the interpretation of lesions in toxicity studies.

Animals↗
PubMed2004

Targeting WNT, protein kinase B, and mitochondrial membrane integrity to foster cellular survival in the nervous system.

Targeting essential cellular pathways that determine neuronal and vascular survival can foster a successful therapeutic platform for the treatment of a wide variety of degenerative disorders in the central nervous system. In particular, oxidative cellular injury can precipitate several nervous system disorders that may either be acute in nature, such as during cerebral ischemia, or more progressive and chronic, such as during Alzheimer disease. Apoptotic injury in the brain proceeds through two distinct pathways that ultimately result in the early externalization of membrane phosphatidylserine (PS) residues and the late induction of genomic DNA fragmentation. Degradation of DNA may acutely impact cellular survival, while the exposure of membrane PS residues can lead to microglial phagocytosis of viable cells, cellular inflammation, and thrombosis in the vascular system. Through either independent or common pathways, the Wingless/Wnt pathway and the serine-threonine kinase Akt serve central roles in the maintenance of cellular integrity and the prevention of the phagocytic disposal of cells "tagged" by PS exposure. By selectively governing the activity of specific downstream substrates that include GSK-3beta, Bad, and beta-catenin, Wnt and Akt serve to foster neuronal and vascular survival and block the induction of programmed cell death. Novel to Akt is its capacity to protect cells from phagocytosis through the direct modulation of membrane PS exposure. Intimately linked to the activation of Wnt signaling and Akt is the maintenance of mitochondrial membrane potential and the regulation of Bcl-xL, mitochondrial energy metabolism, and cytochrome c release that can lead to specific cysteine protease activation.

Animals↗
PubMed1992

The histopathology of different foreign-body reactions in oral soft tissue and bone tissue.

Foreign bodies may be endogenous or exogenous and provoke chronic inflammation of the foreign-body type. The reaction provides a mechanism for elimination of the foreign body and the reaction pattern depends on the kind of tissue involved. In soft tissues there is cellular inflammation and fibrous encapsulation with macrophages. In bone, during the healing period, biomechanical factors determine whether a fibrous encapsulation or a bony covering develops demarcating the foreign material. The particular characteristics of the foreign-body reaction in bone explain the success of dental and orthopaedic implants.

Animals↗
PubMed2004

Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 are involved in both excitotoxin-induced neurodegeneration and regeneration.

Intrahippocamal injections of kainic acid (KA) significantly increase the expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) in the ipsilateral hippocampus at 2-4 h and 21-45 days post-administration, suggesting the possible involvement of these chemokines in both neurodegenerative and regenerative processes. To examine the possible role of these chemokines on neuronal cell death, hippocampal neurons were incubated with either MCP-1 or MIP-2 in vitro and examined to assess the effects on neuronal cell viability. These treatments resulted in significant neuronal apoptosis that could be abrogated by prior treatment with the caspase-1 inhibitor, Z-VAD-FMK, the caspase-3 inhibitor, Z-DEVD-FMK, the Galphai inhibitor, pertussis toxin, or the MAO-B inhibitor, (-)deprenyl. Furthermore, this chemokine apoptotic effect could also be observed in vivo as intrahippocampal injections of MCP-1 or MIP-2 resulted in the apoptosis of hippocampal neurons, thus supporting a direct role of these chemokines in neuronal death. In contrast, immunohistological analysis of kainic acid lesions on days 21-45 revealed significant expression of MCP-1 and MIP-2 associated with reactive astrocytes and macrophages, respectively, with no apoptotic populations being observed. These results suggested that these chemokines might also mediate distinct biological effects on local microenvironmental cell populations at various stages post truama and during cellular repair. To address this possibility, astrocyte were cultured in the presence or absence of these chemokines and examined by microarray analysis for effects on astrocytes gene expression. A number of genes encoding proteins associated with inflammation, cellular signaling, differentiation, and repair were directly modulated by chemokine treatment. More specifically, the RNA and protein expression of the neurotrophic factor, basic fibroblast growth factor (bFGF), was found to be significantly increased upon culture with MCP-1 and MIP-2. Conditioned media derived from chemokine-stimulated astrocytes also facilitated bFGF-dependent neuronal cell differentiation and promoted survival of H19-7 neurons in vitro, suggesting a possible role for chemokine-activated astrocytes as a source of trophic support. Taken together, these data support possible autocrine and paracrine roles for MCP-1 and MIP-2 in both the "death and life" of hippocampal neurons following CNS injury.

Animals↗
PubMed2004

Signaling the brain in systemic inflammation: role of sensory circumventricular organs.

The sensory circumventricular organs (CVOs) are specialized brain regions that lack a tight blood-brain barrier. A role for these brain structures in signaling the brain during systemic inflammation is based on the following sets of observations. In spite of some conflicting data from literature, lesions of CVOs have been shown to block several components of brain controlled illness responses (i.e. fever or neuroendocrine modifications). Receptors for inflammatory cytokines and for bacterial fragments are constitutively expressed in cells within the sensory CVOs. The expression of most of these receptors is upregulated under conditions of systemic inflammation. Cellular responses in theses brain areas can be recorded and documented after stimulation of these respective receptors. Such responses include changes in electrical activity of neurons, induction of transcription factors leading to modifications in gene expression during inflammation and to a localized release of secondary signal molecules. These molecules may influence or even gain access to neural structures inside the blood-brain barrier, which can normally not directly be reached by circulating cytokines or bacterial fragments.

Animals↗
PubMed2026

Mechanotransduction in musculoskeletal mesenchymal tissues: implications for bone, tendon, and cartilage regenerative engineering-a narrative review.

PURPOSE/AIM OF THE STUDY: To integrate evidence on how mechanical signals regulate musculoskeletal connective-tissue biology and how cellular context and loading history shape mechanotransduction and mechanical memory. MATERIALS AND METHODS: This narrative review synthesized PubMed-indexed evidence on extracellular matrix mechanics, adhesion complexes, the cytoskeleton, nucleus, primary cilia, mechanosensitive ion channels, cell state, and loading history in bone, tendon, ligament, and cartilage. RESULTS: Mechanotransduction is best understood as a coupled extracellular matrix-integrin-cytoskeleton-nucleus continuum rather than as independent cytoskeletal or nuclear drivers. Responses are conditioned by lineage stage, anatomic niche, inflammation, cellular subpopulation, and prior mechanical exposure. Mechanical memory may be encoded through persistent YAP/TAZ activity, microRNA programs, DNA methylation, histone modifications, chromatin architecture, and metabolic remodeling. Evidence is strongest for bone, including Piezo-dependent osteogenesis, TRPV4-mediated shear sensing, viscoelastic compression, osteocyte-stromal extracellular-vesicle signaling, and osteogenesis-angiogenesis coupling. Tendon and ligament require anisotropic architecture and strain-window control, whereas cartilage shows a narrow distinction between physiologic TRPV4-associated anabolism and high-strain or inflammation-sensitized Piezo/YAP-mediated maladaptation. CONCLUSIONS: Translational implications include mechanically defined cell expansion, biomaterial preconditioning, stage-specific rehabilitation, and potency assays incorporating loading history. Direct clinical validation of stable perioperative cellular mechanical memory remains limited. Future studies should combine controlled mechanical perturbation with bulk and single-cell RNA sequencing, chromatin-accessibility profiling, spatial methods, and perturbational genomics.

Mechanotransduction↗
PubMed2005

Neutrophilic inflammation and IL-8 levels in induced sputum of alpha-1-antitrypsin PiMZ subjects.

BACKGROUND: Severe alpha-1-antitrypsin deficiency (AATD), due to homozygosity for the protease inhibitor (Pi) Z allele, is a genetic risk factor for chronic obstructive pulmonary disease (COPD). In a previous study the sputum of severe AATD subjects with airflow obstruction showed a pattern of cellular inflammation similar to COPD patients. It is uncertain whether heterozygotes for the Z allele or intermediate deficiency (PiMZ) have an increased risk of developing COPD. METHODS: Sputum cell counts and the supernatant level of the neutrophil chemoattractant interleukin (IL)-8 were investigated by sputum induction in 10 non-smoker asymptomatic PiMZ subjects with normal pulmonary function, 10 patients with stable COPD, and 10 age matched normal subjects. Data are expressed as mean (SD). RESULTS: The mean (SD) number of neutrophils was significantly higher (p<0.01) in the sputum of PiMZ subjects (84.5 (22.2) x10(4)/ml) and patients with COPD (126.9 (18.8) x10(4)/ml) than in matched normal subjects (55.0 (8.7) x10(4)/ml). IL-8 levels were increased in PiMZ subjects (828.5 (490.6) ng/ml; median 1003.0 ng/ml; range 1260-100 ng/ml) and in COPD patients (882.5 (524.3) ng/ml; median 934.9 ng/ml; range 1506-258 mg/ml) compared with normal subjects (3.5 (0.5) ng/ml; median 3.5 ng/ml; range 4.5-2.5 ng/ml). There was a significant positive correlation between IL-8 supernatant concentration and neutrophil count in PiMZ subjects (p = 0.036; r = 0.66). An inverse correlation was observed between the percentage of neutrophils and forced expiratory volume in 1 second (% predicted) in patients with COPD (p = 0.04; r = -0.43). CONCLUSIONS: These findings indicate that PiMZ subjects without airflow obstruction may have an IL-8 related neutrophilic inflammation in the airways, similar to stable COPD patients, suggesting an increased risk of developing pulmonary changes.

Aged↗
PubMed1997

The inflammatory effects of 2 ppm NO2 on the airways of healthy subjects.

Nitrogen dioxide (NO2) is a free radical and a common oxidant in polluted air. Here we present data on the time course of inflammation after NO2 exposure, as reflected in bronchial biopsy and airway lavage specimens. Healthy, nonsmoking subjects were exposed to air or 2 ppm NO2 for 4 h in random order on separate occasions. Endobronchial biopsies, bronchial washing (BW), and bronchoalveolar lavage (BAL) were done at 1.5 h (n = 15) or 6 h (n = 15) after exposure. In BW, exposure to NO2 induced a 1.5-fold increase in interleukin-8 (IL-8) (p < 0.05) at 1.5 h and a 2.5-fold increase in neutrophils (p < 0.01) at 6 h. In BAL fluid (BALF), small increases were observed in CD45RO+ lymphocytes, B-cells, and natural killer (NK) cells only. Immunohistologic examination of bronchial biopsy specimens showed no signs of upregulation of adhesion molecules, and failed to reveal any significant changes in inflammatory cells at either time point after NO2 exposure. In summary, NO2 induced a neutrophilic inflammation in the airways that was detectable in BW at 6 h after NO2 exposure. The increase in neutrophils could be related to the enhanced IL-8 secretion observed at 1.5 h after exposure. The absence of adhesion-molecule upregulation or cellular inflammation in mucosal biopsy specimens indicates that the major site of inflammation following exposure to NO2 may be in the smaller airways and not in the alveoli.

Adult↗