EDU PRETREATMENT DECREASES POLYMORPHONUCLEAR LEUKOCYTE MIGRATION INTORAT LUNG AIRWAYS

Pretreatment with the heterocyclic compound EDU -[2-(2-oro-1-imidazoli ndinyl)ethyl]-N'-phenylurea) has previously been shown to reduce polym orphonuclear leukocyte (PMN) infiltration into the airways of ozone-ex posed rats. The present study further examined the effects of 1 and 2 days EDU pretreatment on rat lung inflammatory responses by determinin g PMN infiltration in response to intratracheal instillation with the chemoattractant formyl-norleucine-leucine-phenylalanine (fNLP). Maxima l recovery of PMNs by bronchoalveolar lavage was observed 4 hr after f NLP instillation with no alteration in the numbers of recoverable macr ophages and lymphocytes. Although 1-day pretreatment with EDU did not affect PMN recovery from fNLP-instilled rat lungs, 2 days of EDU pretr eatment prevented PMN infiltration as indicated by PMN recoveries that were similar to those obtained from saline-instilled lungs. Measureme nts of lung-marginated and interstitial pools of inflammatory cells us ing collagenase tissue digestion demonstrated no effect of 2 days EDU pretreatment. Although 2 days EDU pretreatment alone did not alter blo od PMN content, lung permeability, and the lavage recoveries of inflam matory cells, blood PMN responses to chemotactic stimuli in vitro were impaired. In addition, EDU was shown to directly inhibit PMN chemotax is and superoxide anion generation in vitro. These data demonstrated t hat EDU acts by interfering with PMN activation and migration rather t han by decreasing PMN availability. EDU, by modulating the inflammator y response, represents a useful compound for preventing PMN-associated amplification of acute lung injuries. (C) 1994 Academic Press, Inc.