INTERACTION OF HUMAN NEUTROPHILS WITH AIRWAY EPITHELIAL-CELLS - REDUCTION OF LEUKOTRIENE B-4 GENERATION BY EPITHELIAL-CELL DERIVED PROSTAGLANDIN E-2

Airway epithelial cells (AEC) play an active role in the regulation of inflammatory airway disease. In the present study we analyzed the int eraction of AEC with polymorphonuclear leukocytes (PMN) in coincubatio n with respect to their arachidonic acid (AA) metabolism using reverse d phase-HPLC and post-HPLC-ELISA. Primary cultures of porcine AEC rele ased predominantly PGE(2), PGF(2a), and 15-hydroxyeicosatetraenoic aci d (15-HETE), whereas the major human PMN-derived AA metabolite was the chemotactic factor leukotriene B-4 (LTB4). In AEC-PMN cocultures stim ulated with the calcium ionophore A23187, PMN-related 5-lipoxygenase p roducts were decreased by 45%. This reduction in LTB4 formation in the presence of AEC was mainly due to PGE, generated by the epithelial ce lls, whereas 15-HETE made a minor contribution. Most of the effect was inhibited by AEC pretreatment with acetylsalicylic acid and restored by addition of equivalent amounts of exogenous PGE(2). LTB4 degradatio n was not enhanced in PMN-AEC coincubations. Moreover, reduction of LT B4 formation in this system did not require an intimate cell-to-cell c ontact as shown by studies involving filter membranes for PMN-AEC sepa ration. Superoxide anion concentrations were also decreased in PMN-AEC coincubations; this effect, however, was unrelated to PCE, for quanti tative reasons and was probably due to O-2(-) degradation by epithelia l cells. In summary, epithelially derived PCE2 is the major mediator i n the coincubation of porcine AEC and human PMN that downregulates neu trophil responses by activating receptors on the neutrophil. A minor c ontributor in this course of PMN-AEC interaction may be the 15-HETE tr anscellular pathway. Overall, airway epithelium appears to play an ant iinflammatory role by damping the proinflammatory potential of neutrop hils. (C) 1998 Wiley-Liss, Inc.