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Interaction of human neutrophils with airway epithelial cells: Reduction of leukotriene B 4 generation by epithelial cell derived prostaglandin E 2
Author(s) -
Klockmann Martin Till Ulrich,
Jahn HansUlrich,
Hippenstiel Stefan,
Krämer HansJoachim,
Suttorp Norbert
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199806)175:3<268::aid-jcp4>3.0.co;2-m
Subject(s) - leukotriene b4 , transcellular , arachidonic acid , chemotaxis , leukotriene , respiratory epithelium , prostaglandin e2 , eicosanoid , chemistry , thromboxane a2 , metabolite , lipid signaling , hydroxyeicosatetraenoic acid , prostaglandin e , epithelium , immunology , biochemistry , receptor , inflammation , biology , endocrinology , enzyme , genetics , asthma
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 PGE 2 , PGF 2a , and 15‐hydroxyeicosatetraenoic acid (15‐HETE), whereas the major human PMN‐derived AA metabolite was the chemotactic factor leukotriene B 4 (LTB 4 ). In AEC‐PMN cocultures stimulated with the calcium ionophore A23187, PMN‐related 5‐lipoxygenase products were decreased by 45%. This reduction in LTB 4 formation in the presence of AEC was mainly due to PGE 2 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 PGE 2 . LTB 4 degradation was not enhanced in PMN‐AEC coincubations. Moreover, reduction of LTB 4 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 PGE 2 for quantitative reasons and was probably due to 2 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. J. Cell. Physiol. 175:268–275, 1998. © 1998 Wiley‐Liss, Inc.