Project Title:   Cellular and molecular studies of inorganic arsenic-induced deficiencies in the innate immune system

 

 

Principal Investigator:  Antonio J. Planchart, PhD.

Assistant Professor

Department of Biological Sciences

North Carolina State University

ajplanch@ncsu.edu

 

Co-Investigators:          Carolyn J. Mattingly, Ph.D.

Associate Professor

Department of Biological Sciences

North Carolina State University

cjmattin@ncsu.edu

 

David Reif, Ph.D.

Associate Professor

Department of Biological Sciences

North Carolina State University

dmreif@ncsu.edu

 

Jeffrey Yoder, PhD.

Associate Professor

Department of Molecular Biomedical Sciences

College of Veterinary Medicine

North Carolina State University

jayoder@ncsu.edu

 

Abstract: Toxicity from exposure to naturally occurring inorganic arsenic in drinking water is a significant global health threat. Chronic arsenic exposure is associated with teratogenicity and increased levels of morbidity and mortality manifested by heightened risks to certain cancers, innate immune deficiencies, hypertension and stroke, diabetes and respiratory diseases. Despite the immune risks associated with arsenic toxicity, there have been very few advances in our understanding of immunity-related cellular and molecular mechanisms affected by arsenic exposure. The objective of the proposed multidisciplinary research is to investigate effects of chronic exposure to low concentrations of inorganic arsenic (10 and 100 parts per billion) on the cellular and molecular functions of macrophages and neutrophils, which form essential components of the innate immune system. These experiments will be performed primarily in an in vivo setting by leveraging specific immune properties of embryonic- and larval-stage zebrafish (Danio rerio). Early-stage zebrafish rely exclusively on innate immunity to defend from external challenges. This property, along with rapid development from egg to larvae, developmental transparency, and availability of transgenic lines expressing fluorescent macrophages and neutrophils, make zebrafish a superior model for studies of immune function. Successful completion of the aims in this proposal will result in a substantial increase in our knowledge of the role of arsenic toxicity in immune deficiencies, will pave the way for more comprehensive explorations of how arsenic alters molecular pathways important in immune function, and will establish the utility of innovative in vivo assays for research of a broader chemical space.