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Results for “Cellular inflammation”

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PubMed1997

Histologic correlates of angiographic chronic total coronary artery occlusions: influence of occlusion duration on neovascular channel patterns and intimal plaque composition.

OBJECTIVES: Age-related changes in histologic composition and neovascular channel (NC) pattern of angiographic chronic total coronary artery occlusions (CTOs) were studied to define histologic correlates of age-related revascularization profiles and neovascular channel formation. BACKGROUND: Revascularization of CTOs is frequently characterized by inability to cross or dilate the lesion and a high incidence of reocclusion or restenosis but low periprocedural ischemic complication rates. Little is known about the histopathologic basis of these observations. METHODS: Ninety-six angiographic CTOs from autopsy studies in 61 patients who had undergone coronary angiography within 3 months of death were studied. Abrupt plaque rupture was excluded. Occlusion segments were analyzed for 1) histologic composition as a function of lesion age; and 2) NC pattern as a function of lesion age and intimal plaque (IP) composition. RESULTS: Cholesterol and foam cell-laden IP was more frequent in younger lesions (p = 0.0007), whereas fibrocalcific IP increased with CTO age (p = 0.008). IP NCs arose directly from adventitial vasa vasorum and were anatomically and quantitatively related in terms of number and size (p = 0.0001) to the extent of IP cellular inflammation. IP cellular inflammation exceeded that found in the adventitia (p < 0.001) or media (p = 0.0001) across all CTO ages. In CTOs < 1 year old, the adventitia was associated with a larger number and size of NCs relative to the IP (p = 0.0006 and p = 0.009), media (p = 0.0001 and p = 0.002) and recanalized lumen (p = 0.0001 and p = 0.001). In CTOs >1 year old, the adventitia and IP NC numbers were similar and exceeded NC numbers found in the media (p = 0.0001) and recanalized lumen (p = 0.0001 and p = 0.003). CONCLUSIONS: Angiographic CTO frequently corresponds to less than complete occlusion by histologic criteria. Age-related changes in IP composition from cholesterol laden to fibrocalcific may explain the adverse revascularization profile of older CTOs. IP NC growth derived from the adventitia increases with age and is strongly associated with IP cellular inflammation. IP NC formation may protect against the flow-limiting effects of IP growth.

Adult↗

PubMed2003

Role of nitric oxide in chronic allergen-induced airway cell proliferation and inflammation.

Chronic cellular inflammation and airway wall remodeling with subepithelial fibrosis and airway smooth muscle thickening are features of chronic asthma. We determined the role of nitric oxide in the pathogenesis of allergen-induced airway cell proliferation and inflammation by studying the effects of a relatively selective prodrug inhibitor of nitric-oxide synthase type 2 (NOS2), L-N6-(1-iminoethyl)-lysine-5-tetrazole amide (SC-51). Brown-Norway rats were sensitized to ovalbumin and were exposed to ovalbumin aerosol every 3rd day on six occasions and were treated orally with either vehicle or SC-51 (10 mg. kg(-1); 12 doses). We measured inflammatory cell accumulation in the airways and proliferation of cells by incorporation of bromodeoxyuridine. There was an increase in the total number of airway smooth muscle cells expressing bromodeoxyuridine from 1.3% of airway smooth muscle cells in saline exposed to 5.4% after allergen-exposure (P < 0.001) and airway epithelial cells from 3.3 cells/mm basement membrane to 9.6 after allergen-exposure (P < 0.001). SC-51 had no effect on airway smooth muscle or epithelial cell proliferation. SC-51 attenuated the allergen-induced increase in major basic protein (MBP+) eosinophil (P < 0.05) and CD4+ T-cell (P < 0.05) accumulation. We conclude that nitric oxide derived during allergic inflammation is involved in the expression of eosinophilic inflammation and not in epithelial or airway smooth muscle cell DNA synthesis induced by chronic allergen exposure.

Actins↗

PubMed2004

Cellular FLIP long form-transgenic mice manifest a Th2 cytokine bias and enhanced allergic airway inflammation.

Cellular FLIP long form (c-FLIP(L)) is a caspase-defective homologue of caspase-8 that blocks apoptosis by death receptors. The expression of c-FLIP(L) in T cells can also augment extracellular signal-regulated kinase phosphorylation after TCR ligation via the association of c-FLIP(L) with Raf-1. This contributes to the hyperproliferative capacity of T cells from c-FLIP(L)-transgenic mice. In this study we show that activated CD4(+) T cells from c-FLIP(L)-transgenic mice produce increased amounts of Th2 cytokines and decreased amounts of Th1 cytokines. This correlates with increased serum concentrations of the Th2-dependent IgG1 and IgE. The Th2 bias of c-FLIP(L)-transgenic CD4(+) T cells parallels impaired NF-kappa B activity and increased levels of GATA-3, which contribute, respectively, to decreased IFN-gamma and increased Th2 cytokines. The Th2 bias of c-FLIP(L)-transgenic mice extends to an enhanced sensitivity to OVA-induced asthma. Taken together, these results show that c-FLIP(L) can influence cytokine gene expression to promote Th2-driven allergic reaction, in addition to its traditional role of blocking caspase activation induced by death receptors.

Adjuvants, Immunologic↗

PubMed2025

Cellular Inflammation-Induced Cleavage of Phosphorothioate DNA Locker Activates CRISPR/Cas9 Regulator for Gene Editing.

The CRISPR technology is a highly promising strategy for developing a versatile toolbox to engineer genetic circuits. However, achieving precise and specific control over the activity of the CRISPR/Cas9 system in response to intracellular processes remains a challenging endeavor. In this study, we present a cellular inflammation-induced activation of an engineered CRISPR/Cas9 regulator for gene regulation. A phosphorothioate (PS)-modified DNA sequence, referred as the "locker," is employed to deactivate single guide RNA (sgRNA), whose locker sequence complements the spacer region of sgRNA. In the presence of myeloperoxidase during cellular inflammation, a halogenation process is triggered, leading to the generation of HClO, specifically cleaving the PS site of locker and activating CRISPR/Cas9 for gene editing. The target GFP gene has been successfully edited, downregulating the GFP protein expression in HeLa cells. This study provides valuable insights into the CRISPR-based gene regulation through specific endogenous processes.

Humans↗

PubMed1996

Subchronic inhalation of high concentrations of low toxicity, low solubility particulates produces sustained pulmonary inflammation and cellular proliferation.

Long-term inhalation exposures to high dust burdens can produce tumors or proliferative keratin cysts in the lungs of exposed rats. We hypothesized that dust burdens which overwhelm lung clearance mechanisms are associated with sustained cellular proliferation responses and pulmonary inflammation. Male rats were exposed to titanium dioxide (TiO2) or carbonyl iron (CI) particles for 4 weeks at concentrations of 5, 50 and 250 mg/m3. Following completion of exposure, the lungs of sham and dust-exposed animals were lavaged or assessed for cell proliferation or particle clearance immediately after, as well as 1 week, 1, 3 and 6 months postexposure. Exposures to TiO2 or CI at 250 mg/m3 produced persistent pulmonary inflammatory responses and increased BrdU labeling of terminal airway and pulmonary parenchymal cells. The results of this study clearly demonstrate that exposure to excessive dust concentrations of two low toxicity, low solubility particle-types produced sustained pulmonary inflammation, enhanced pulmonary cell labeling, impairment of particle clearance, and the development of pulmonary lesions.

Administration, Inhalation↗

PubMed2001

Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study.

Insulin resistance, which is highly prevalent in the elderly, is suggested to be accompanied by an increased acute phase response. Until now, it is unclear whether cellular adhesion molecules are involved in the clustering of insulin resistance. In the present study, we examined the relationship of insulin resistance (measured by postload insulin) with levels of markers of inflammation and cellular adhesion molecules in a random sample of 574 nondiabetic elderly men and women participating in the Rotterdam Study. Associations were assessed by regression analysis, with ln-insulin as the dependent variable [regression coefficient (95% confidence interval)]. In our population, insulin was strongly and significantly (P < 0.001) associated with the markers of inflammation C-reactive protein [1.52 (0.96-2.08)], alpha-1-antichymotrypsin [1.25 (0.82-1.69)], and IL-6 [2.60 (1.69-3.52)], adjusted for age and gender. Associations weakened, to some extent, after additional adjustment for measures of obesity, smoking, and cardiovascular disease. Insulin was associated with the soluble intercellular adhesion molecule 1 [2.22 (1.29-3.16; P < 0.001)], whereas no association with the soluble vascular cell adhesion molecule 1 was found. The strength of the associations of insulin with C-reactive protein, alpha-1-antichymotrypsin, IL-6, and soluble intercellular adhesion molecule 1, as assessed by standardized regression coefficients, was comparable with the strength of the associations of insulin with high-density lipoprotein cholesterol, body mass index, and waist-to-hip ratio. The results of this population-based study indicate that low-grade inflammation and the cellular adhesion molecule soluble intercellular adhesion molecule 1 are an integral part of insulin resistance in nondiabetic elderly. These factors may contribute to the well-known relationship between insulin resistance and cardiovascular disease risk and might potentially become therapeutic targets in insulin resistant subjects.

Aged↗

PubMed2002

Effect of heparin in the irrigation solution on postoperative inflammation and cellular reaction on the intraocular lens surface.

PURPOSE: To evaluate the influence of heparin sodium in the irrigation solution on postoperative inflammation and cellular reaction on the anterior surface of a hydrophilic intraocular lens (IOL). SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This randomized prospective single-surgeon study included 50 patients with senile cataract only. Half the patients received 1 mL of heparin sodium (concentration 10 IU/mL) in addition to the regular irrigating solution. In all other respects, the procedure was standardized: clear corneal incision, phacoemulsification, and implantation of a Hydroview foldable hydrogel IOL (Bausch & Lomb). The parameters of inflammation-anterior chamber flare and cells-were evaluated with the pupil dilated in a masked fashion using a Kowa FC-1000 laser flare-cell meter 1, 3, 7, 14, and 28 days and 3, 6 and 12 months postoperatively. The cellular reaction was semiquantitatively examined and analyzed by specular microscopy. RESULTS: In both groups, flare and cell values increased on the first postoperative day and successively decreased thereafter. In the first week, the flare and cell values were significantly higher in the group without heparin sodium in the irrigating solution. Subsequently, there were no differences between the 2 groups in flare or cells. At 1 day, the heparin sodium group had statistically significantly fewer IOLs with no cells on the surface. Subsequently, no differences in cellular reaction on the IOL were observed. CONCLUSIONS: Heparin sodium added to the standard irrigating solution reduced disturbances of the blood-aqueous barrier in the early postoperative period. There seemed to be no long-term effect, especially on cellular reaction, on the hydrophilic IOL surface.

Aged↗

PubMed1991

Influence of lens cortex on postoperative inflammation and cellular deposits on surface of intraocular lenses in rabbit eye.

An animal model was used to evaluate the influence of residual lens cortex on postoperative inflammation and cellular deposits on intraocular lenses (IOLs). Eighteen New Zealand white rabbits underwent bilateral endocapsular phacoemulsification with placement of a one-piece polymethylmethacrylate (PMMA) IOL in the capsular bag. A predetermined amount (15 mg, 30 mg or 60 mg) of homogenized lens cortex was injected into the anterior chamber of one of the eyes of each rabbit after bilateral IOL implantation. The contralateral eye served as the control. The animals underwent slit-lamp examination postoperatively, and the anterior segment of each eye was examined by gross and light microscopy. On slit-lamp examination, the eyes which had received a 60-mg injection of cortex showed a significantly higher amount of posterior synechiae than their contralateral, control eyes. After 2 weeks of observation, the rabbits were sacrificed, the eyes were enucleated, and the IOLs were removed and examined by light microscopy and scanning electron microscopy (SEM). The number of cellular deposits on the IOLs removed from the eyes receiving a 30-mg injection of cortex was significantly larger than that found in their contralateral, control eyes (P less than 0.05), but the eyes in the 60-mg and 15-mg injection groups showed no significant difference between control eyes and IOL eyes in the number of cellular deposits on explanted IOLs. Observation by SEM determined that the filopodia on the epithelioid cells found on the IOLs removed from the eyes in the 60-mg injection group showed an increased number and length compared to their controls. The epithelioid cells on the IOLs of the 30-mg injection group showed an increased number of filopodia compared to their controls.

Animals↗

PubMed1996

Rescue of HSV-1 neurovirulence is associated with induction of brain interleukin-1 expression, prostaglandin synthesis and neuroendocrine responses.

Several HSV-1 neurovirulence genes have been mapped but the mechanisms by which they affect host-virus interactions are not known. We have previously mapped HSV-1 neurovirulence to the UL53 gene region of the viral DNA by transfer of this gene from the neurovirulent R-19 strain to the non-neurovirulent R-15 strain in the generation of the p-71 recombinant, in which neurovirulence was rescued. In the present study we inoculated these strains into the paraventricular nucleus (PVN) of the hypothalamus of rats. We examined: (1) Clinical course of encephalitis. (2) Hypothalamic-pituitary-adrenocortical (HPA) axis function. (3) Brain cytokine gene mRNA expression and prostaglandin E2 (PGE2) production. (4) The relation of these parameters to viral replication and to cellular inflammation. In R-15 infected rats no signs of disease were observed. There was a temporary inflammatory reaction and IL-1 beta transcription in the PVN area. The function of the HPA axis was similar to control rats. Only slight increase in brain PGE2 production was found. In R-19 and p-71 infected rats, overt clinical signs of encephalitis and cellular inflammation in the PVN area were observed within 3 days post-infection (p.i). All rats died between 4-7 days p.i. These strains induced IL-1 beta transcription in the hypothalamus as well as in extra-hypothalamic brain regions in which no cellular inflammation was found. Basal serum ACTH and' CS were markedly elevated and hypothalamic CRF-41 content was significantly reduced as compared to R-15 infected rats. Both strains markedly increased brain PGE2 production. HSV-1 brain titers at 3 days p.i. were 100-fold lower than the inoculum titer although clinical signs of encephalitis were prominent. The results suggest that rescue of HSV-1 neurovirulence by the UL53 gene region of the viral genome is associated with enhancement of viral-induced brain IL-1 beta gene expression, increased brain PGE2 synthesis and hypersecretion of HPA axis hormones. Viral-induced brain derived cytokines and prostaglandins may contribute to the clinical syndrome of acute herpetic encephalitis in particular at early stages of the disease when virus load in the brain is low and cellular infiltrates are not widespread.

Adrenocorticotropic Hormone↗

PubMed2003

Effects of transdermal and oral estrogen supplementation on endothelial function, inflammation and cellular redox state.

The incidence of ischemic heart disease shows a sharp rise after menopause. However, the effects of hormone replacement therapy (HRT) on cardiovascular disease are still controversial. Not only oxidative stress, but also inflammation has been suggested to play an important role in the pathogenesis of cardiovascular events. We compared the effects of HRT on endothelial function, cellular antioxidant system and inflammation between oral and transdermal administration in mild hypercholesterolemic postmenopausal women. Transdermal estradiol replacement was administrated to 12 patients (mean age 53 years) for 12 weeks, and oral conjugated equine estrogen was administrated to 12 patients (mean age 54 years) for 12 weeks. The flow-mediated endothelium-dependent dilation of the brachial artery, serum levels of thioredoxin as a marker of the cytoprotective antioxidant system, and high-sensitivity C-reactive protein (hs-CRP) were measured every 4 weeks. The flow-mediated vasodilation increased with HRT (oral, baseline 4.9 +/- 0.5, 4-week 8.9 +/- 0.7*, 8-week 9.9 +/- 0.6*, 12-week 9.4 +/- 0.7*; transdermal, 4.7 +/- 0.6, 8.3 +/- 0.7*, 9.1 +/- 0.8*, 8.9 +/- 0.9%*, * = p < 0.01 versus baseline). The thioredoxin levels decreased with HRT (oral, 26.1 +/- 7.2, 24.1 +/- 8.2, 22.1 +/- 7.8, 19.1 +/- 7.0*; transdermal, 26.9 +/- 7.4, 23.4 +/- 8.7, 21.1 +/- 7.9, 19.2 +/- 7.2 ng/ml*, * = p < 0.01 versus baseline). There were no differences in the variation of the flow-mediated vasodilation or thioredoxin concentrations between the 2 groups. The hs-CRP levels increased with oral HRT (0.32 +/- 0.12, 0.72 +/- 0.17*, 0.86 +/- 0.23*, 0.88 +/- 0.21 mg/dl*, * = p < 0.01 versus baseline), while transdermal HRT did not elicit any changes (0.35 +/- 0.15, 0.34 +/- 0.17, 0.38 +/- 0.20, 0.36 +/- 0.22 mg/dl). The differences of hs-CRP concentrations between the 2 groups analyzed by 2-way ANOVA were significant (p < 0.01). Oral HRT instigated inflammation, but transdermal did not. Both oral and transdermal HRT, however, improved endothelial function and decreased oxidative stress through affecting the cellular redox state. These differentials in the effects caused by the course of administration may affect the future cardiovascular events.

Administration, Cutaneous↗

PubMed2005

Monosodium urate and calcium pyrophosphate dihydrate (CPPD) crystals, inflammation, and cellular signaling.

Monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals are responsible for acute synovial inflammation but also contribute to cartilage degradation and bone lesions within the joint. They activate multiple signal transduction pathways leading to cell activation and recruitment. Some signalling pathways are activated by both types of crystals, and other pathways may only be activated by one type depending on cell type, namely neutrophils, monocytes, macrophages, synovial fibroblasts, endothelial cells and chondrocytes. Cascades of activated proteins involve cytoplasmic membrane related proteins (FAK complex, Src family tyrosine kinases), but also MAPK and NF-kB pathways, leading to NO, prostanoid and cytokine production, and protease activation. This review will also focus on potential therapeutic targets related to cellular signalling in MSU and CPPD crystal-induced inflammation.

Animals↗

PubMed2002

Effect of nitrogen dioxide on ovalbumin-induced allergic airway disease in a murine model.

The effect of exposure to irritant air pollutants on the development of allergic airway disease is poorly understood. This study examines the effects of the lower respiratory tract irritant, NO(2), on the outcome of ovalbumin (OVA)-induced allergic airway disease. Male and female C57Bl/6 mice were sensitized by weekly intraperitoneal (ip) OVA injections for 3 wk followed by daily 1-h OVA aerosol inhalation challenge for 3 or 10 d. Initially, mice were exposed daily for 3 d to air or 0.7 or 5 ppm NO(2) for 2 h following each OVA aerosol challenge. OVA exposure resulted in pronounced lower airway inflammation, as evidenced by a significant increase in bronchoalveolar lavage (BAL) total cellularity and eosinophil levels. BAL eosinophil levels were significantly lower in OVA-NO(2) compared to OVA-air animals. The reduction was similar at both NO(2) exposure concentrations. In a subsequent study, sensitized animals were exposed for 3 or 10 d to aerosolized OVA followed by air or 0.7 ppm NO(2). BAL eosinophils were again reduced at 3 d by OVA-NO(2) exposure compared to OVA-air mice. At 10 d the eosinophilia was virtually abolished. This reduction in OVA-induced cellular inflammation by NO(2) was confirmed by histopathological analysis. Contrary to expectations, exposure to NO(2) during the aerosol challenge to OVA dramatically diminished the outcome of allergic disease in lungs as measured by airway cellular inflammation.

Aerosols↗

PubMed2003

Allergen-induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N-terminal kinase.

Chronic cellular inflammation and airway wall remodelling with subepithelial fibrosis and airway smooth muscle (ASM) cell hyperplasia are features of chronic asthma. Jun N-terminal kinase (JNK) may be implicated in these processes by regulating the transcriptional activity of activator protein (AP)-1. We examined the effects of an inhibitor of JNK, SP600125 (anthra [1,9-cd] pyrazole-6 (2 H)-one), in a model of chronic allergic inflammation in the rat. Rats sensitised to ovalbumin (OA) were exposed to OA-aerosol every third day on six occasions and were treated with SP600125 (30 mg kg-1 b.i.d; 360 mg in total) for 12 days, starting after the second through to the sixth OA exposure. We measured eosinophilic and T-cell inflammation in the airways, proliferation of ASM cells and epithelial cells by incorporation of bromodeoxyuridine (BrdU), and bronchial responsiveness to acetylcholine. SP600125 significantly reduced the number of eosinophils (P<0.05) and lymphocytes (P<0.05) in bronchoalveolar lavage fluid, suppressed eosinophilic (P<0.05) and CD2+ T-cell (P<0.05) infiltration within the bronchial submucosa, and the increased DNA incorporation in ASM (P<0.05) and epithelial cell incorporation (P<0.05). SP600125 did not alter bronchial hyper-responsiveness observed after chronic allergen exposure. Pathways regulated by JNK positively regulate ASM cell proliferation and allergic cellular inflammation following chronic allergen exposure.

Actins↗

PubMedDate not supplied

Cellular imaging of inflammation in atherosclerosis using magnetofluorescent nanomaterials.

OBJECTIVE: Magnetofluorescent nanoparticles (MFNPs) offer the ability to image cellular inflammation in vivo. To better understand their cellular targeting and imaging capabilities in atherosclerosis, we investigated prototypical dextran-coated near-infrared fluorescent MFNPs in the apolipoprotein E-deficient (apo E-/-) mouse model. METHODS AND RESULTS: In vitro MFNP uptake was highest in activated murine macrophages (p < .001). Apo E-/- mice (n = 11) were next injected with the MFNP (15 mg/kg iron) or saline. In vivo magnetic resonance imaging (MRI) demonstrated strong plaque enhancement by the MFNPs (p < .001 vs. saline), which was confirmed by multimodality ex vivo MRI and fluorescence reflectance imaging. On fluorescence microscopy, MFNPs were found in cellular-rich areas of atheroma and colocalized with immunofluorescent macrophages over endothelial cells and smooth muscle cells (p < .001). CONCLUSIONS: Here we show that (1) the in vitro and in vivo cellular distribution of atherosclerosis-targeted MFNPs can be quantified by using fluorescence imaging methods; (2) in atherosclerosis, dextranated MFNPs preferentially target macrophages; and (3) MFNP deposition in murine atheroma can be noninvasively detected by in vivo MRI. This study thus provides a foundation for using MFNPs to image genetic and/or pharmacological perturbations of cellular inflammation in experimental atherosclerosis and for the future development of novel targeted nanomaterials for atherosclerosis.

Animals↗

PubMedDate not supplied

Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes.

Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28%) was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

Adult↗

PubMed1992

Early hepatic stages of Plasmodium berghei: release of circumsporozoite protein and host cellular inflammatory response.

After injection of Plasmodium berghei sporozoites into Norway-Brown rats, we were able to localize these sporozoites and the early hepatic trophozoites developing from them in histological sections of the liver stained with a sensitive immunogold-silver procedure. Sporozoites invading hepatocytes released substantial quantities of circumsporozoite protein into the hepatocyte cytoplasm. This intrahepatic cytoplasmic distribution reached a maximal level at about 4 h post-sporozoite injection. As the hepatic parasites continued to differentiate, circumsporozoite protein became undetectable within the cytoplasm of the hepatocytes and became localized around the periphery of each parasite. There was generalized cellular inflammation within the liver of the host, which first became evident at around 4 h post-sporozoite injection and progressed to the formation of well-defined granulomas by 24 h. Such histopathological changes were not seen in rats injected with killed sporozoites, indicating that the cellular inflammation was induced by viable, infective sporozoites. We did not observe cellular infiltration specifically associated with any of the developing hepatic stages that we observed, even up to 28 h post-sporozoite inoculation. These results indicate that viable sporozoites induced rapid and generalized hepatic inflammation in host rats. However, sporozoites that successfully invaded hepatocytes and then proceeded to develop further did not appear to be the target of inflammatory cells until a period beginning at around 40 h post-sporozoite inoculation.

Acute-Phase Reaction↗

PubMed1989

Role for T lymphocytes in silica-induced pulmonary inflammation.

The role of the immune system in modulating pulmonary damage evoked by exposure to silica crystals has been examined in a mouse model of experimental silicosis. Congenitally T cell-deficient mice (Balb/c nu/nu) were compared with T cell sufficient mice (Balb/c nu/+) in the degree of silica-induced cellular inflammation on days 3, 5, 7, 30, and 60 after an intratracheal instillation of silica. Cellular inflammation was assessed by increases in the total number and type of inflammatory cell in lung lavage fluid and in lung tissue. Inflammation and/or injury were also measured in the lavage fluid by increases in total protein, angiotensin-converting enzyme and plasminogen activator. No significant difference existed between the two types of mice in total lavage cell number or total protein. In nu/+ mice, the neutrophil predominated early, followed by the macrophage as the major inflammatory cell. However, in nu/nu mice, the neutrophil remained the predominant inflammatory cell throughout the two months postinjection. In addition, angiotensin-converting enzyme levels remained elevated in the nu/nu animals above those in the nu/+ mice whereas plasminogen activator was elevated early (before day 7) in both, and decreased comparably over time. These data suggest that T cells directly or indirectly influence the maintenance of a macrophage infiltrate and the termination of a neutrophil response after exposure to silica. However, it appears that neither T cells nor the cells they influence affect the ultimate amount of collagen deposition.

Animals↗

PubMed2006

Airway inflammation and cellular stress in noneosinophilic atopic asthma.

STUDY OBJECTIVES: It has been suggested that patients with noneosinophilic asthma (NEA) show increased numbers of sputum neutrophils and a lack of response to therapy with corticosteroids, which are features that are commonly related to COPD. The aim of our study was to test the hypothesis that airway inflammation in NEA patients is different from that seen in patients with eosinophilic asthma (EA) and is similar to COPD. DESIGN: Sputum cellular stress markers and neutrophilic and eosinophilic fluid-phase mediators were analyzed in asthma and COPD patients. NEA patients were identified based on a sputum eosinophil count of < or = 2.2% of the total nonsquamous cell count, and were compared to EA and COPD patients. SETTING: University Hospital of Heraklion, Department of Thoracic Medicine. PATIENTS: A total of 37 atopic asthmatic patients and 25 patients with COPD. MEASUREMENTS: Sputum cell counts, cellular expression of heme oxygenase-1, inducible nitric oxide synthase, and nitrotyrosine, and sputum levels of eosinophilic cationic protein (ECP), myeloperoxidase (MPO), interleukin-8, and granulocyte macrophage colony-stimulating factor. RESULTS: A total of 17 asthmatic patients (46%) belonged to the NEA group and 20 patients (54%) to the EA group. Patients with NEA showed no difference in neutrophil counts, fluid-phase mediators, or cellular stress markers compared to patients with EA. Compared to COPD patients, NEA patients showed the following significant differences: lower total cell counts (p < 0.03); lower neutrophil counts (p < 0.01); lower nitrotyrosine positive cell counts (p < 0.003); lower ECP levels (p < 0.005); lower MPO levels (p < 0.000); higher lymphocyte counts (p < 0.01); and higher macrophage counts (p < 0.03). CONCLUSIONS: Despite low eosinophil counts, airway inflammation in NEA patients may share common features with that in EA patients but is distinct from COPD. Larger studies are needed to investigate further the clinical and inflammatory characteristics of NEA before we are able to categorize asthma patients into those with or without eosinophilic inflammation.

Aged↗