SEARCH · Search PubMed

Results for “ASBESTOSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,495 records · Page 83Linked to original sources

PubMed1991

Tumorigenicity of fine man-made fibers after intratracheal administrations to hamsters.

Six types of man-made fibers were administered intratracheally (2.0 mg/animal each a week, for 5 weeks; total 10 mg/animal) to female Syrian hamsters that were observed histologically for 2 years after administration. The fibers were rock wool [average diameter (D) = 6.1 microns, average length (L) = 296 microns], fiberglass (D = 0.65 microns, L = 16.8 microns), potassium titanate fiber (D = 0.36 microns, L = 7.17 microns), calcium sulfate fiber (D = 1.0 microns, L = 17.8 microns), basic magnesium sulfate fiber (D = 0.45 microns, L = 22.4 microns), and metaphosphate fiber (D = 2.38 microns, L = 64.1 microns). Tumors were observed in hamsters that had received basic magnesium sulfate fiber (9/20), metaphosphate fiber (6/20), calcium sulfate fiber (3/20), and fiberglass (2/20) but not in the control, rock wool, or potassium titanate fiber groups. The primary sites of the tumors were not only in the pleural cavity but also in the intracelial organs, kidney, adrenal gland, bladder, and uterus. Only a few of the tumors were identified as mesotheliomas by histological examination. In addition to neoplastic lesions, fibrosis, pleural thickening, and chronic inflammatory changes in the lungs were observed in the hamsters, but these changes appeared too mild to foster a pneumoconiosis such as asbestosis.

Administration, Inhalation↗

PubMed2003

Impaired cardiac autonomic functions in patients with environmental asbestos exposure: a study of time domain heart rate variability.

Environmental asbestos exposure is related to diffuse pleural disease (thickening and calcification) and restrictive pulmonary disease. To assess cardiac autonomic system, we investigated the time domain heart rate variability (HRV) by Holter monitoring and their correlation with pulmonary function tests in patients with pleural disease caused by environmental asbestos exposure. We studied 45 patients (26 men, 19 women, aged 62.67 +/- 10.1 years) and 35 healthy patients who had similar sex and age profile to the patients (24 men, 11 women, aged 59.31 +/- 8.4 years). The asbestosis group was divided into 3 subgroups according to the severity of forced vital capacity (FVC) severe (group 1) (n = 12): FVC less than 50% of expected, moderate (group 2) (n = 16): FVC 64%-51% of expected and mild (group 3) (n = 17): FVC 65%-80% of expected. HRV parameters were significantly different among all groups (P<.0001). Comparing the 4 groups (subgroups and control group), group 1 had the lowest mean HRV values and controls had the highest mean HRV values (P<.0001). Severity of autonomic dysfunction was correlated with the severity of FVC and arterial oxygen pressure. Right ventricular end-diastolic internal diameter (RVEDID) and right ventricular end-systolic internal diameter (RVESID) values were significantly increased in patients (P <.0001, P < 0.0001, respectively). Pulmonary acceleration time (AcT) values were shorter in all patient groups than control group (P <.0001). It was shortest in group 1. Group 2 and 3 had shorter AcT values than control group. HRV parameters were correlated positively with AcT values and negatively with RVEDID and RVESID values. In conclusion, patients with restrictive pulmonary disease due to environmental asbestos exposure had autonomic dysfunction, which was correlated with the severity of restriction. This was thought to be the result of chronic hypoxia, pulmonary hypertension, and right ventricular enlargement.

Analysis of Variance↗

PubMed2003

Asbestos: old foe in 21st century developing countries.

While use of asbestos materials in developed nations has been decreasing because of the harmful health effects of asbestos dust mining, processing and use of the ancient material in developing countries is increasing. The regulatory mechanism for use, handling and disposal of asbestos and associated waste in developing countries are weak and information on asbestos-related diseases is scanty but emerging. We identify lack of epidemiological data on asbestos health effects as a major gap to be bridged in the promotion of occupational and environmental health in developing countries. Without data on local situations, diseases such as asbestosis and mesothelioma remain too obscure to assist the campaign for appropriate regulation of asbestos usage or attracting attention to abominable industrial practices generally.

Asbestos↗

PubMed2002

Chronic immune activation and inflammation in the pathogenesis of AIDS and cancer.

Infection with the human immunodeficiency virus (HIV) invariably leads to the development of acquired immunodeficiency syndrome (AIDS) in most infected humans, yet does so rarely, if at all, in HIV-infected chimpanzees. The differences between the two species are not due to differences in cellular receptors or an inability of the chimpanzee to be infected, but rather to the lack of pan-immune activation in the infected primate. This results in reduced apoptotic death in CD4+ T-helper lymphocytes and a lower viral load. In humans the degree of chronic immune activation correlates with virus load and clinical outcome with high immune activation leading to high viral loads and the more rapid progression to AIDS and death. The type of immune perturbation seen in HIV-associated AIDS is similar to that of chronic graft-versus-host disease (GVHD) where reduced cell-mediated immune (CMI) responses occur early in the course of the disease and where humoral responses (HI) predominate. A reduced CMI response occurs in a number of chronic infectious diseases, including tuberculosis and leishmaniasis. More recently, it has become increasingly apparent that the CMI response is suppressed in virtually all malignant diseases, including melanoma and colorectal and prostate cancer. This raises the possibility that, as the malignant process develops, the cancer cells evolve to subvert the CMI response. Moreover, the reduced CMI response seen in colorectal cancer (CRC) patients is completely reversed following curative surgery strongly supporting the hypothesis that CRC can suppress the systemic immune response. Wound healing, ovulation, embryo implantation, and fetal growth are all associated with suppressed CMI and neovascularization (the formation of new blood vessels) or angiogenesis (the formation of new blood vessels from an existing vasculature). If unresolved, wound healing results in chronic inflammation, which can give rise to the phenomenon of "scar cancers." Indeed all the chronic inflammatory conditions known to be associated with the subsequent development of malignant disease, including chronic obstructive airway disease (COPD), ulcerative colitis (UC), and asbestosis, give rise to similar proangiogenic, suppressed CMI, and HI-predominant environments. In keeping with this CMI-associated cytokines such as interleukin (IL)-2 and interferon (IFN)-gamma tend to be antiangiogenic, whereas HI cytokines such as IL-6 tend to be proangiogenic. Furthermore, chronic immune activation leads to the synthesis and release of factors such as macrophage inflammatory protein (MIP)-1 that inhibit apoptosis through suppression of p53 activity. The "Golden Triangle" of suppressed CMI, angiogenesis, and reduced apoptosis would provide the ideal environment for the serial mutations to occur that are required for the development of malignant disease. If the observed association is relevant to carcinogenesis, then treatments aimed at reducing the components of these inflammatory conditions may be useful both in the setting of chemoprevention and the therapeutic management of established disease.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Free radical activity of natural and heat treated amphibole asbestos.

The amphibole minerals amosite and crocidolite were subjected to calcination and to hydrothermal treatment in order to study the effect of these heat treatments on the ability of the minerals to trigger formation of free radicals, which is known to be a main factor causing asbestosis and other asbestos-induced diseases. Free radical activity of the natural and heat treated minerals was studied by using supercoiled DNA (pUC18 plasmid) as a target molecule, and also by means of EPR spectroscopy. It was shown that after calcination of the natural minerals at 1073 K their free radical activity was strongly decreased These results, which may have relevant consequences for asbestos technology, were correlated with concomitant alteration of the structure and surface chemistry of the minerals during calcination.

Asbestos, Amosite↗

PubMed2003

Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases.

Exposure to asbestos causes cellular damage, leading to asbestosis, bronchogenic carcinoma, and mesothelioma in humans. The pathogenesis of asbestos-related diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicated that asbestos fibers generate reactive oxygen and nitrogen species (ROS/RNS) and cause oxidation and/or nitrosylation of proteins and DNA. The ionic state of iron and its ability to be mobilized determine the oxidant-inducing potential of pathogenic iron-containing asbestos types. In addition to their capacity to damage macromolecules, oxidants play important roles in the initiation of numerous signal transduction pathways that are linked to apoptosis, inflammation, and proliferation. There is strong evidence supporting the premise that oxidants contribute to asbestos-induced lung injury; thus, strategies for reducing oxidant stress to pulmonary cells may attenuate the deleterious effects of asbestos.

Animals↗

PubMed1993

Systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is the most common of the connective tissue disorders and can involve virtually any organ in the body. It is associated with pleuropulmonary manifestations in well over 50% of cases. Pleuritis with or without pleural effusion is the most common manifestation and can be particularly troublesome to manage but is rarely life-threatening. More serious manifestations in the lung include acute lupus pneumonitis with or without alveolar haemorrhage, chronic lupus pneumonitis and pulmonary hypertension. These all contribute significantly to overall mortality in SLE. The association between SLE and the antiphospholipid syndrome, leading to venous thrombosis and pulmonary embolism, is well recognized. Up to 20% of all cases of SLE present in childhood and many of these have pulmonary features at presentation or during the course of their illness. Sepsis is one of the main causes of death in SLE and pulmonary sepsis in these often immunocompromised patients contributes a significant proportion. Several drugs can produce a clinical syndrome that has many of the clinical and immunological features of SLE. Pleuritis may be seen in up to half of these cases of drug induced SLE. The development of SLE and conditions such as sarcoidosis or asbestosis in the same patient may represent a simple coincidence but there is some evidence for a closer association between these disorders.

Humans↗

PubMed1997

Distinction between pleural mesothelioma and pulmonary adenocarcinoma using MOC31 in an asbestos sprayer.

Asbestos exposure may cause asbestosis, pleural plaques and benign pleural disease, and may pre-dispose to malignant mesothelioma and other neoplasms. The occurrence to two primary tumours in the same patient is rare, and the appearance of a pleural mesothelioma and another lung tumour is exceptional. The present case report describes a patient who, by standard immunohistochemistry, was thought to have mesothelioma at pleuro-pneumonectomy, and adenocarcinoma in the other lung at post-mortem 5 months later. Subsequent investigation using the MOC31 antibody demonstrated a single pathology of adenocarcinoma of the lung. The additional use of this antibody has important histopathological and legal implications.

Adenocarcinoma↗

PubMed1998

Adenocarcinoma simulating mesothelioma: a clinicopathologic and immunohistochemical study of 29 cases.

We report 29 cases of adenocarcinomas whose clinical, gross, and microscopic appearance resembled diffuse malignant pleural mesothelioma. Initial criteria for inclusion in the study included availability of an open pleural biopsy or decortication specimen and microscopic evidence of neutral (periodic acid-Schiff positive) mucin in the tumor. The median age of the patients was 63 years (range, 31 to 78 years), with a peak age in the seventh decade. There were 24 men and five women. Thirteen of them had a history of smoking; six (21%) had possible or definite occupational exposure to asbestos. Three (21%) of 14 lung specimens showed ferruginous bodies and two (14%) showed microscopic evidence of asbestosis. At least 25 patients had pleural effusion, most typically unilateral. Needle biopsy of pleura showed malignancy in 10 (77%) of 13 cases. Most (20 of 29) patients underwent pleural stripping. Radiotherapy and chemotherapy was each given to three patients without effect. Median survival by Kaplan-Meier estimate was 8 months, with an 18-month survival of 13%. Histologically, glands (23 cases), nests (13 cases), tubulopapillary arrays (12 cases), or sheets (eight cases) of tumor cells were found. Spindling of neoplastic cells was seen in 10% of cases. Three (21%) of 14 lung specimens showed a subpleural adenocarcinoma. Antibodies to polyclonal CEA, Ber-EP4, Leu-M1, and B72.3 were positive in 94%, 56%, 50%, and 44% of cases, respectively. All but one of the cases stained with two or more of the antibodies CEA, Ber-EP4, Leu-M1, or B72.3. This study indicates that adenocarcinomas simulating mesothelioma are aggressive variants of peripheral adenocarcinomas with a poor prognosis, that they can show pathological evidence of asbestos exposure in a subset of cases, and that immunohistochemical and histochemical stains are useful in their differential diagnosis with diffuse malignant mesotheliomas.

Adenocarcinoma↗

PubMed2004

Prior lung disease and risk of lung cancer in a large prospective study.

OBJECTIVES: While 75-90% of people who develop lung cancer are smokers, only a small proportion of smokers develop lung cancer. Identifying factors that increase a smoker's risk of developing lung cancer may help scientists to better understand the etiology of lung cancer and more effectively target high-risk groups for screening. METHODS: Information on physician-diagnosed non-malignant lung diseases [asbestosis, asthma, chronic bronchitis or emphysema (CB/E), pneumonia, and tuberculosis] was obtained at baseline from 17,698 men and women involved in CARET, a randomized lung cancer prevention trial of beta-carotene and vitamin A among heavy smokers and asbestos-exposed workers. Hazard ratios for lung cancer were estimated through Cox regression models, after controlling for potential confounding factors, included smoking. Analyses were restricted to former and current smokers. RESULTS: During a median follow up of 9.1 years, 1028 cases of lung cancer occurred. Those who developed lung cancer were more likely to report a history of CB/E than controls (adjusted HR = 1.29, 95% CI: 1.09-1.53). In subgroup analyses, the association between a history of CB/E and lung cancer was stronger for those who were younger at diagnosis/reference, men in the heavy smoker cohort, former smokers, and those with squamous cell carcinomas. There was little association between a history of other lung diseases and lung cancer. CONCLUSIONS: Smokers with a history of CB/E may be at higher risk of developing lung cancer, independent of their smoking history.

Adult↗

PubMed1999

p53 protein, EGF receptor, and anti-p53 antibodies in serum from patients with occupationally derived lung cancer.

The oncogene product epidermal growth factor receptor (EGF-R), the tumour suppressor gene product p53 and anti-p53 antibodies are detectable in the serum of certain cancer patients. Increased levels of some of these products were reported in lung cancer patients after occupational asbestos exposure and after exposure to polycyclic aromatic hydrocarbons or vinylchloride. In the first step, this study investigated the possible diagnostic value of serum EGF-R, p53-protein and anti-p53 antibodies, measured by an enzyme-linked immunosorbent assay, in lung tumour patients. In addition to being investigated on a molecular epidemiological basis, these parameters were examined as biomarkers of carcinogenesis, especially with regard to asbestos incorporation effects or of radon-induced lung cancers. Also, a possible effect of cigarette smoking and age dependence were studied. A total of 116 male patients with lung or pleural tumours were examined. The histological classification was four small-cell cancers, six large-cell cancers, 32 adenocarcinomas, 47 squamous carcinomas, 12 mixed lung carcinomas, five diffuse malignant mesotheliomas and ten lung metastasis of extrapulmonary tumours. Twenty-two lung cancers and all mesotheliomas were related to asbestos, 22 lung cancers were related to ionizing radiation and 61 patients had cigarette smoke-related lung cancer. Besides these patients 50 male patients with non-malignant lung or pleural diseases were included; of the latter eight subjects suffered from asbestosis. Controls were 129 male subjects without any lung disease. No significantly elevated or decreased serum values for p53 protein, EGF-R, or anti-p53 antibodies as a function of histological tumour type, age, or degree and type of exposure (asbestos, smoking, ionizing radiation) could be found. The utility of p53-protein, EGF-R and anti-p53 antibodies as routine biomarkers for screening occupationally derived lung cancers is limited.

Adenocarcinoma↗

PubMed2003

Unusual intraparenchymal growth patterns of malignant pleural mesothelioma.

AIMS: Malignant pleural mesothelioma is known to mimic morphologically a number of diverse reactive and neoplastic conditions. We describe three unusual intraparenchymal growth patterns of malignant mesothelioma seen in a series of 200 malignant pleural mesotheliomas. The diagnostic pitfalls associated with these findings are described and their potential medico-legal implications are highlighted. METHODS AND RESULTS: The study group comprised 200 malignant pleural mesotheliomas. In each case diagnosis was morphologically confirmed with ancillary immunohistochemistry using a broad panel of both mesothelial and epithelial markers. The patterns of intraparenchymal growth were documented and grouped as: direct subpleural; lymphangitic; and other. The 200 malignant pleural mesotheliomas comprised 118 epithelioid, 57 biphasic and 25 sarcomatoid, subtyped according to the WHO classification. Direct subpleural invasion was seen in 42 cases, lymphangitic spread in 27 cases. Other less well-defined intraparenchymal patterns included three sarcomatoid subtype malignant mesotheliomas exhibiting an intra-alveolar growth pattern mimicking epithelioid haemangioendothelioma. One epithelioid subtype malignant mesothelioma contained an intraparenchymal tumour nodule microscopically comprising lepidic spread of neoplastic cells over maintained alveolar structures mimicking bronchioloalveolar carcinoma. One epithelioid subtype malignant mesothelioma morphologically had areas in which alveoli were distended by discohesive epithelioid neoplastic cells with no interstitial invasion. The appearances mimicked desquamative interstitial pneumonia. Immunohistochemistry played an important role in the definitive diagnosis of each unusual parenchymal tumour deposit. In 126 malignant mesotheliomas no invasion of the subjacent lung parenchyma was identified. CONCLUSIONS: An awareness of the unusual parenchymal growth pattern in malignant mesothelioma is important to prevent misdiagnosis of other entities. In the medico-legal setting, the presence of epithelioid haemangioendothelioma or bronchioloalveolar carcinoma (in the absence of asbestosis) may be deemed to impact upon the patient's anticipated life expectancy and thereby would decrease the compensation settlement.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2002

Positron emission tomography imaging in nonmalignant thoracic disorders.

The role of the fluorodeoxyglucose (FDG) technique positron emission tomography (PET) is well established in the management of patients with lung cancer. Increasingly, it is becoming evident that FDG-PET can be effectively employed to diagnose a variety of benign pulmonary disorders. Knowledge of such applications further expands the domain of this powerful modality and further improves the ability to differentiate benign from malignant diseases of the chest. We describe pertinent technical factors that substantially contribute to optimal imaging of the thoracic structures. Particularly, the complementary role of attenuation correction (AC) to that of non-AC images is emphasized. We further outline the need for and the state of the art for co-registration of PET and anatomic images for diagnostic and therapeutic purposes. We then review patterns of physiologic uptake of FDG in thoracic structures, including the lung, the heart, the aorta and large arteries, esophagus, thymus, trachea, thoracic muscles, bone marrow, and joints and alterations following radiation therapy to the thorax. A great deal of information is provided with regard to differentiating benign from malignant nodules and in particular, we emphasize the role of dual time point imaging and partial volume correction for accurate assessment of such lesions. Following a brief review of the diagnostic issues related to the assessment of mediastinal adenopathies, the role of FDG-PET imaging in environment-induced lung diseases, including pneumoconiosis, smoking, and asthma are described. A large body of information is provided about the role of this technology in the management of patients with suspected infection and inflammation of the lungs such as acquired immunodeficiency syndrome, fever of unknown origin, sarcoidosis, chronic granulomatous disease and monitoring the disease process and response to therapy. Finally, the value of FDG-PET in differentiating benign from malignant diseases of the pleura including asbestosis-related disorders is described at the conclusion of this comprehensive review.

Animals↗

PubMed2001

Asbestos causes apoptosis in alveolar epithelial cells: role of iron-induced free radicals.

Asbestos causes asbestosis and malignancies by mechanisms that are not fully understood. Alveolar epithelial cell (AEC) injury by iron-induced reactive oxygen species (ROS) is one important mechanism. To determine whether asbestos causes apoptosis in AECs, we exposed WI-26 (human type I-like cells), A549 (human type II-like cells), and rat alveolar type II cells to amosite asbestos and assessed apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine-5'-triphosphate-biotin nick end labeling (TUNEL) staining, nuclear morphology, annexin V staining, DNA nucleosome formation, and caspase 3 activation. In contrast to control medium and TiO2, amosite asbestos and H2O2 each caused AEC apoptosis. A role for iron-catalyzed ROS was suggested by the finding that asbestos-induced AEC apoptosis and caspase 3 activation were each attenuated by either an iron chelator (phytic acid and deferoxamine) or a.OH scavenger (dimethyl-thiourea, salicylate, and sodium benzoate) but not by iron-loaded phytic acid. To determine whether asbestos causes apoptosis in vivo, rats received a single intratracheal instillation of amosite (5 mg) or normal saline solution, and apoptosis in epithelial cells in the bronchoalveolar duct regions was assessed by TUNEL staining. One week after exposure, amosite asbestos caused a 3-fold increase in the percentage of apoptotic cells in the bronchoalveolar duct regions as compared with control (control, 2.1% +/- 0.35%; asbestos, 7.61% +/- 0.15%; n = 3). However, by 4 weeks the number of apoptotic cells was similar to control. We conclude that asbestos-induced pulmonary toxicity may partly be caused by apoptosis in the lung epithelium that is mediated by iron-catalyzed ROS and caspase 3 activation.

Animals↗

PubMed1975

Physical parameters of airborne asbestos fibres in various work environments-preliminary findings.

The results of a pilot investigation to describe the physical parameters, length, aspect ratio, mass and shape of airborne fibres in a variety of industries producing processing and handling chrysotile, amosite and crocidolite are described. Samples of airborne dust were collected on nucleopore membrane filters and examined by scanning electron microscopy. The diameters and lengths of airborne fibres collected during the dumping of raw amosite at an asbestos products plant were greater than those of fibres collected during the application of amosite insulation. Chrysotile fibres collected in the carding area of an asbestos textile plant also tended to have smaller diameters than fibres collected in the dryer and bagging areas of an asbestos mill. The measurements of fibre dimensions indicate that the degree of protection afforded a worker by optical counts using the membrane filter technique is likely to depend on variety of asbestos and stage of processing. Preliminary results are not in conflict with experimental data suggesting that asbestosis might be related to the mass of airborne dust and primary malignant mesothelial tumors to exposure to fibres in a specific range of fibre diameter and length.

Air Pollutants↗

PubMedDate not supplied

Comparison of methods of assessing asbestos fiber concentrations.

Dimensional measurement of the counted fibers has important implications for setting of environmental standards to protect workers' health. Results of fiber concentrations as determined by different methods were compared. Each method was used to determine concentration by examining one sector of membrane filter on which fibrous dust was collected in various workplaces. The concentrations measured by the Asbestos International Association (AIA) method for 35 samples were, on the average, greater than the concentrations determined by the modified British Occupational Hygiene Society--Asbestosis Research Council (BOHS-ARC) method. The AIA and modified BOHS-ARC methods were found to be linearly correlated (r = 0.82). The mean of total fiber concentrations obtained by using the indirect transmission electron microscopy (TEM) method was 15.5 times the mean obtained by using the direct TEM method. The difference in concentrations determined by the two TEM methods resulted from disintegration of fiber bundles into single fibers during the ashing and ultrasonifying processes used in the indirect method. At least 83.5% of total fibers observed by TEM escaped detection by phase contrast microscopy.

Air Pollutants, Occupational↗

PubMed1990

Screening for lung cancer. Is it worthwhile?

Prevention of lung cancer remains the best method of decreasing lung cancer mortality. Patients who smoke should be urged to quit, and children, teenagers, and young adults must not begin smoking. At high risk are smokers, especially those under 40 years of age who may have smoked two to four packs of cigarettes per day for 20 years; persons who have had a previous lung cancer; patients with bullous emphysema; patients with asbestosis; and patients with evidence of chronic airflow obstruction. Although radiographic screening may detect lung cancer earlier and lead to increased 5-year survival rates, it does not reduce lung cancer mortality rates.

Adolescent↗

PubMed2000

In vitro cleavage by asbestos fibers of the fifth component of human complement through free-radical generation and kallikrein activation.

Chrysotile and crocidolite fibers incubated in normal human plasma (NHP) generated from the C5 component of complement C5a-type fragments that stimulated polymorphonuclear leukocyte (PMN) chemotaxis. Absorption of NHP with antiserum against C5a totally abolished neutrophil chemotactic activity. Asbestos fibers also produced C5a small peptides in the presence of ethylene glycol bis(beta-aminoethyl ether) N,N,N'N'-tetraacetic acid (EGTA) but not ethylene diamine tetraacetic acid (EDTA). Activation of C5 was significantly inhibited when asbestos fibers were pretreated with iron chelators such as sodium dithionite (DTN), deferoxamine (DFX), or ascorbate (AA). Concentration-related inhibition of C5 activation was also observed when asbestos fibers were added concurrently to plasma in the presence of DFX, 1,3-dimethyl-2-thiourea (DMTU), a strong hydroxyl scavenger, or aprotinin (APR), a specific protease inhibitor. Further, chrysotile and crocidolite significantly increased plasma kallikrein activity. Data demonstrate that asbestos-induced C5 activation plays a role in inflammatory reactions characteristic of asbestosis through mechanisms involving iron ions, hydroxyl radicals, and oxidized C5-ike fragments. The ferrous ions present at the asbestos fiber surface trigger this activation and catalyze, via Fenton reaction, the production of hydroxyl radicals, which in turn convert native C5 to an oxidized C5-like form. This product is then cleaved by kallikrein, activated by the same asbestos fibers, yielding an oxidized C5a with the same functional properties as C5a.

Adult↗