Pulmonary & Respiratory Medicine

Disparate Species-Dependent Leukocyte Behavior before and after Adding an Elastase Inhibitor

Abstract

Nicholas J Cheronis, Nathan A Groathouse, Richard A Bowen, Sanford R Simon, John C Cheronis and John E Repine

Animal models are often used to identify aspects of the pathophysiology and to develop new therapeutic interventions for human disorders. Leukocyte serine elastases are key mediators of inflammation and meaningful therapeutic targets because of their potential contributions to the Acute Respiratory Distress Syndrome (ARDS) and other inflammatory disorders. We compared the extracellular matrix degrading and bactericidal activities against both Escherichia coli and Staphylococcus aureus, of leukocytes from humans, dogs, hamsters, rats, pigs and rabbits before and after adding highly selective serine elastase inhibitors. Not surprisingly, we found significant species-dependent differences in both activities and the responses to adding serine elastase inhibitors. Our results reinforce the need for care in selecting the optimal animal species for evaluating both the underlying pathophysiology of inflammatory diseases and potential new interventions being developed to treat these conditions.