Lipopolysaccharide enhances substance P-mediated neutrophil adherence to epithelial cells and cytokine release

Han Pin Kuo, Horng Chyuan Lin, Kou Hsiung Hwang, Chun Hua Wang, Ling Chuan Lu

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


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-1β) and tumor necrosis factor (TNF-α) 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-1β and TNF-α release from A549 cells either spontaneously or stimulated by SP or LPS. LPS + SP significantly enhanced IL-1β and TNF-α 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 + SPenhanced IL-1β and TNF-α release. Pretreatment with the serine protease inhibitor cocktail also inhibited LPS + SP-enhanced neutrophil adherence-dependent IL-1β and TNF-α release as well as their mRNA expression. In conclusion, we have demonstrated LPS enhanced SP-mediated neutrophil adherence and associated IL-1β and TNF-α release from the A549 epithelial monolayer, partly through NK-1 receptors. Neutrophil adherence to epithelial cells may release serine protease to induce IL-1β and TNF-α release and their synthesis.

Original languageEnglish
Pages (from-to)1891-1897
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number5
Publication statusPublished - Jan 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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