Nitric Oxide as an Immune Effector Molecule of Bivalves: Modulation by Environmental ChemicalsEPA 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: Biology/Life Sciences , Health , Ecosystems
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Approach:NO and nitric oxide synthase (NOS) activity will be measured in control hemocytes and in hemocytes withdrawn from contaminant-exposed oysters, or in cells exposed in vitro.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.