title: Interaction of human neutrophils with airway epithelial cells: reduction of leukotriene B4 generation by epithelial cell derived prostaglandin E2.
abstract: Airway epithelial cells (AEC) play an active role in the regulation of inflammatory airway disease. In the present study we analyzed the interaction of AEC with polymorphonuclear leukocytes (PMN) in coincubation with respect to their arachidonic acid (AA) metabolism using reversed phase-HPLC and post-HPLC-ELISA. Primary cultures of porcine AEC released predominantly PGE2, PGF2a, and 15-hydroxyeicosatetraenoic acid (15-HETE), whereas the major human PMN-derived AA metabolite was the chemotactic factor leukotriene B4 (LTB4). In AEC-PMN cocultures stimulated with the calcium ionophore A23187, PMN-related 5-lipoxygenase products were decreased by 45%. This reduction in LTB4 formation in the presence of AEC was mainly due to PGE2 generated by the epithelial cells, 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 PGE2. LTB4 degradation was not enhanced in PMN-AEC coincubations. Moreover, reduction of LTB4 formation in this system did not require an intimate cell-to-cell contact as shown by studies involving filter membranes for PMN-AEC separation. Superoxide anion concentrations were also decreased in PMN-AEC coincubations; this effect, however, was unrelated to PGE2 for quantitative reasons and was probably due to O2- degradation by epithelial cells. In summary, epithelially derived PGE2 is the major mediator in the coincubation of porcine AEC and human PMN that downregulates neutrophil responses by activating receptors on the neutrophil. A minor contributor in this course of PMN-AEC interaction may be the 15-HETE transcellular pathway. Overall, airway epithelium appears to play an antiinflammatory role by damping the proinflammatory potential of neutrophils.
authors.affiliation: Department of Internal Medicine, Justus-Liebig-University of Giessen, Germany.
authors.forename: M T
authors.initials: MT
authors.lastname: Klockmann
authors.forename: H U
authors.initials: HU
authors.lastname: Jahn
authors.forename: S
authors.initials: S
authors.lastname: Hippenstiel
authors.forename: H J
authors.initials: HJ
authors.lastname: Krämer
authors.forename: N
authors.initials: N
authors.lastname: Suttorp
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology*; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis*; D015289:Leukotrienes / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D013481:Superoxides / Q000032:analysis; D013552:Swine; D014132:Trachea / Q000166:cytology*
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D013481:Superoxides; D007975:Leukotriene B4; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D015232:Dinoprostone; D001241:Aspirin