Hp. Kuo et al., Lipopolysaccharide enhances substance P-mediated neutrophil adherence to epithelial cells and cytokine release, AM J R CRIT, 162(5), 2000, pp. 1891-1897
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.