WHOLE BLOOD ASSAY ANALYSIS OF IMMUNOSTIMULATORY CONSTITUENTS IN ENVIRONMENTAL PARTICULATE MATTER

Endotoxin;Particulate Matter;Whole Blood Assay;Asthma;Exposure Assessment;Environmental Engineering

Negherbon, Jesse PaulScott, Alan L. ;

Johns Hopkins University

关键词: Endotoxin;    Particulate Matter;    Whole Blood Assay;    Asthma;    Exposure Assessment;    Environmental Engineering;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/37987/NEGHERBON-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

The respiratory system is continuously exposed to particulate matter (PM) through the inhalation of polluted air. The composition of this PM includes an array of hazardous constituents derived from anthropogenic (e.g. – combustion) and biological sources (biogenic). A fraction of these biogenic agents are non-infectious microbial components that are often capable of engaging innate immune defense mechanisms and stimulating the release of conserved inflammatory mediators. Thus, this biogenic fraction of PM carries a unique capacity to provoke adverse respiratory inflammation in the absence of an infectious challenge or overt physical injury. Accordingly, an increasing epidemiologic evidence-base associates exposure to biogenic PM with the development (and severity) of non-infectious respiratory disorders, such as chronic bronchitis and obstructive lung disease. However, the integrative methods necessary to evaluate the pro-inflammatory potential of the full matrix of biogenic PM are absent from customary suite of exposure assessment tools. Instead, conventional practice relies on the measurement of individual classes of agents (e.g. – endotoxins) as proxies of pro-inflammatory hazard. This strategy is partly limited by the sheer diversity of stimuli in the environment. The research presented in this dissertation investigates the pro-inflammatory immune responses to PM exposures using novel human whole blood assay (WBA) methods. The human whole blood system carries an extensive array of innate immune defense mechanisms, displays exquisite sensitivity to biologically relevant stimuli, and is amenable to ex vivo stimulation with complex mixtures of agents. This document comprehensively reviews the applicability of the WBA as an exposure assessment tool, and presents two studies in which pro-inflammatory signals of PM were assessed via WBA. The first study used cryopreserved human whole blood to investigate the pro-inflammatory potential of respirable, thoracic, and inhalable PM from broiler poultry housing, where PM is heavily burdened with microbial components. The second study used fresh whole blood from asthmatic and non-asthmatic Peruvian children to evaluate innate immune responses to traffic PM, which has been associated the exacerbation of asthma symptoms. Taken together, this body of research demonstrates the potential of the human WBA to detect hazardous biogenic components in PM, and characterize individual immunologic responses to these complex stimuli.