T-CELLS AND ALVEOLAR MACROPHAGES IN ASBESTOS EXPOSURE
Project Number5R01ES003301-03
Contact PI/Project LeaderSPRINCE, NANCY L.
Awardee OrganizationMASSACHUSETTS GENERAL HOSPITAL
Description
Abstract Text
Asbestos-related diseases are a major public health problem in the United
States. An estimated 14 million individuals have been exposed to asbestos
during their working lives. Asbestos has been causally linked to
interstitial lung disease, pleural fibrosis, lung cancer, mesothelioma and
cancers of the gastrointestinal tract, larynx and possibly kidney.
Preliminary studies suggest that altered immunoregulation may play a role
in the pathogenesis of asbestos-related diseases. Preliminary findings of
increased OKT4+/OKT8+ ratio in peripheral blood of patients with pleural
plaques or asbestosis of the lung and increased OKT8+ in lung tissue of
patients with idiopathic pulmonary fibrosis suggest compartmental shifts of
circulating T8 bearing lymphocytes into tissue. Preliminary findings of
decreased natural killer activity in peripheral blood of subjects with
asbestos exposure suggest decreased immune surveillance which may be
related to carcinogenicity of asbestos. The aim of this prospective
exposure control study is to evaluate further the prevalence of
abnormalities of the cellular immune system in asbestos workers and to
relate those abnormalities to extent of asbestos exposure and to the
presence of asbestos-related diseases. Subjects with low and moderate to
high asbestos exposure and normal controls will be evaluated. The
investigation will characterize lymphocytes and macrophages by virtue of
their reactivity with monoclonal antibodies and by measurements of cell
function. With respect to lymphocytes, in vitro natural killer activity
will be assessed as will immunoglubin production. With respect to
macrophages, assessment of phagocytosis, fibronectin and secretion of
soluble mediators will be performed in lung lavage fluid. As an index of
asbestos exposure, ferruginous body and asbestos fiber counts will be
performed on lung lavage fluid. Fibers will be characterized by elemental
analysis and scanning electron microscopy to elucidate fiber type and
composition. Serial changes in the immune findings will be correlated with
extent of exposure and with clinical manifestations and progression of
disease. Statistical methods to be used are one-way analysis of variance,
contingency table analysis, multiple linear regression, and longitudinal
multivariate analysis. This study will test the validity of measurements
of immunity as an index of severity of clinical disease and extent of
asbestos exposure.
Public Health Relevance Statement
Data not available.
NIH Spending Category
No NIH Spending Category available.
Project Terms
T lymphocyteX ray spectrometryaffinity chromatographyalveolar macrophagesantibody specificityasbestoscellular immunitycellular pathologydensity gradient ultracentrifugationdiagnostic respiratory lavagedrug administration rate /durationflow cytometryfluorescence microscopyhuman subjectimmunoregulationlongitudinal human studylung imaging /visualization /scanninglung neoplasmsmesotheliomamonoclonal antibodyoccupational disease /disorderpathologic processphagocytosisphase contrast microscopypneumoconiosispollution related respiratory disorderprostaglandinspulmonary fibrosis /granulomaquestionnairesradiographyrespiratory disorder diagnosisrespiratory functionrespiratory toxinscanning electron microscopyscintillation spectrometrystatistics /biometry
National Institute of Environmental Health Sciences
CFDA Code
DUNS Number
073130411
UEI
FLJ7DQKLL226
Project Start Date
01-July-1984
Project End Date
30-June-1989
Budget Start Date
01-July-1986
Budget End Date
30-June-1987
Project Funding Information for 1986
Total Funding
$153,316
Direct Costs
$101,117
Indirect Costs
$52,199
Year
Funding IC
FY Total Cost by IC
1986
National Institute of Environmental Health Sciences
$153,316
Year
Funding IC
FY Total Cost by IC
Sub Projects
No Sub Projects information available for 5R01ES003301-03
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