Grantee Research Project Results

Nitric Oxide as an Immune Effector Molecule of Bivalves: Modulation by Environmental Chemicals

EPA Grant Number: R827100
Title: Nitric Oxide as an Immune Effector Molecule of Bivalves: Modulation by Environmental Chemicals
Investigators: Anderson, Robert S.
Institution: University of Maryland Center for Environmental Science
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 1998 through September 30, 2001
Project Amount: $335,064
RFA: Exploratory Research - Environmental Biology (1998) RFA Text | Recipients Lists
Research Category: Aquatic Ecosystems , Biology/Life Sciences , Human Health

Description:

The overall goals are to better understand mechanisms of disease resistance in the Eastern oyster, and to determine the effects of sublethal exposure to aquatic contaminants on these mechanisms. The hypotheses to be tested are that nitric oxide (NO ) plays a significant role in oyster defense mechanisms, and that exposure to environmental chemicals inhibits NO synthesis, thereby reducing host defenses to disease. Exposure to xenobiotics exacerbates progression and severity of important oyster diseases; the underlying mechanisms have yet to be identified.

Approach:

NO and nitric oxide synthase (NOS) activity will be measured in control hemocytes and in hemocytes withdrawn from contaminant-exposed oysters, or in cells exposed in vitro. Colorimetric, enzymatic, and antibody-based assays will be used. Effects of chemical stressors on reactive nitrogen species (RNS) pathway activity will be measured and correlated with progression and lethality of diseases caused by protozoan and bacterial pathogens. Characterization of oyster NOS and its regulation will be carried out using appropriate inhibitors, inductants, agonists, etc. Hemocyte-mediated bactericidal activity and the effect of NOS activity modulation on host defense responses will be measured.

Expected Results:

Critical information on NO as an antimicrobial defense molecule of the Eastern oyster and its sensitivity to environmental chemicals will be provided, leading to better understanding of the observed synergy between pollutant exposure and reduced resistance to infectious diseases. In addition, insight will be gained on the physiological control of RNS pathway activity, the interaction of NO with other defense pathways, the possible roles of NOS stimulators as prophylactic agents for bivalve aquaculture, and the utility of NO synthesis or NOS induction as novel immunological biomarkers of environmental stress.

Improvement in Risk Assessment or Risk Management: Oyster hemocytes are functionally analogous to the monocytes/macrophages of higher animals; modulation of key effector functions (such as those dependent on NO ) impair host defense responses to pathogens. Immunotoxic lesions may be used as predictive and diagnostic indices of the biological effects of environmental chemicals. Assays of immunomodulation are useful in screening for immunotoxic agents, and their use could lead to more informed risk assessments. Because hemocytes are a highly conserved cell type, data generated from their study has good potential for interspecies extrapolation.

Publications and Presentations:

Publications have been submitted on this project: View all 2 publications for this project

Supplemental Keywords:

immunology, pathology, toxicology, Chesapeake Bay, susceptibility, metals, tributyltin, pentachlorophenol, water, estuary, toxic substances., Health, Scientific Discipline, Pathology, Health Risk Assessment, Immunology, Biology, Epidemiology, Biochemistry, Disease & Cumulative Effects, health effects, xenobiotics, modulation by environmental chemicals, biological markers, harmful environmental agents, antibody-based assays, immune response, aquatic contaminants, bivalves, immune system effects, oyster disease models, disease resistance, bacterial pathogens, infectious diseases, exposure assessment

Progress and Final Reports:

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.