The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 1983-1984

Cultured Human Endothelial Cells: Markets for Chemical Irritants

David S. Newcombe, MD
The Johns Hopkins School of Public Health, Baltimore, Maryland

Problem

Changes in blood vessel caliber and permeability are a requisite for most inflammatory reactions. Endothelial cells in culture will be exposed to various chemicals which are representative of classes of chemical irritants, and the release of mediators that can affect blood vessel tone and permeability will be measured. The focus will be to isolate, identify, and quantitate the cyclooxygenase products, prostenoids and leukotrienes. Concentration-response and time-response curves for the released metabolites will be defined. For each class of irritant, the relative potencies of specific irritants in vitro will be compared with their known in vivo potencies.

Impact of the Research

The primary objective of this proposal is to determine whether human endothelial cells in culture exposed to irritants respond with the production of mediators, which act as effectors of an irritant response. Such studies will define the usefulness of human endothelial cells as an in vitro assay system for chemical irritants.