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

Lipopolysaccharide (LPS) is implicated in many respiratory tract inflammato ry diseases. Tachykinins, especially substance P (SP) through the NK-1 rece ptor, mediate leukocyte adhesion to the endothelial or airway epithelial ce lls. Here we assessed the enhancement by LPS of tachykinin-mediated neutrop hil adherence to alveolar epithelial cells, and associated interleukin-l be ta (IL-1 beta) and tumor necrosis factor (TNF-alpha) release. Neutrophil ad herence 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 combinat ion (LPS + SP). Neutrophil adherence to epithelial cells induced IL-1 beta and TNF-alpha release from A549 cells either spontaneously or stimulated by SP or LPS. LPS + SP significantly enhanced IL-1 beta and TNF-alpha release . The NK-1 receptor antagonist L-732,138 inhibited this enhancement respons e. 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-1 beta and TNF-alpha release. Pretreatment with the serin e protease inhibitor cocktail also inhibited LPS + SP-enhanced neutrophil a dherence-dependent IL-1 beta and TNF-alpha release as well as their mRNA ex pression. In conclusion, we have demonstrated LPS enhanced SP-mediated neut rophil adherence and associated IL-1 beta and TNF-alpha release from the A5 49 epithelial monolayer, partly through NK-1 receptors. Neutrophil adherenc e to epithelial cells may release serine protease to induce IL-1 beta and T NF-alpha release and their synthesis.