title: Lipopolysaccharide enhances substance P-mediated neutrophil adherence to epithelial cells and cytokine release.
abstract: Lipopolysaccharide (LPS) is implicated in many respiratory tract inflammatory diseases. Tachykinins, especially substance P (SP) through the NK-1 receptor, mediate leukocyte adhesion to the endothelial or airway epithelial cells. Here we assessed the enhancement by LPS of tachykinin-mediated neutrophil adherence to alveolar epithelial cells, and associated interleukin-1 beta (IL-1beta) and tumor necrosis factor (TNF-alpha) release. Neutrophil adherence to A549 epithelial cell was not increased by LPS (100 ng/ml), or SP (10(-)(12)-10(-)(8) M) alone, but was significantly enhanced by their combination (LPS + SP). Neutrophil adherence to epithelial cells induced IL-1beta and TNF-alpha release from A549 cells either spontaneously or stimulated by SP or LPS. LPS + SP significantly enhanced IL-1beta and TNF-alpha release. The NK-1 receptor antagonist L-732,138 inhibited this enhancement response. Prevention of neutrophil adherence by CD11b/CD18 blocking antibody or by placing a filter on the epithelial monolayer diminished spontaneous or LPS + SP-enhanced IL-1beta and TNF-alpha release. Pretreatment with the serine protease inhibitor cocktail also inhibited LPS + SP-enhanced neutrophil adherence-dependent IL-1beta and TNF-alpha release as well as their mRNA expression. In conclusion, we have demonstrated LPS enhanced SP-mediated neutrophil adherence and associated IL-1beta and TNF-alpha release from the A549 epithelial monolayer, partly through NK-1 receptors. Neutrophil adherence to epithelial cells may release serine protease to induce IL-1beta and TNF-alpha release and their synthesis.
authors.affiliation: Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan. q8828@ms11.hinet.net
authors.forename: H P
authors.initials: HP
authors.lastname: Kuo
authors.forename: H C
authors.initials: HC
authors.lastname: Lin
authors.forename: K H
authors.initials: KH
authors.lastname: Hwang
authors.forename: C H
authors.initials: CH
authors.lastname: Wang
authors.forename: L C
authors.initials: LC
authors.lastname: Lu
mesh_terms: D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000166:cytology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D009504:Neutrophils / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D018821:CD18 Antigens; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D064729:Neurokinin-1 Receptor Antagonists; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C086089:3,5-bis(trifluoromethyl)benzyl N-acetyltryptophan; D013373:Substance P; D014364:Tryptophan