Hc. Lin et al., Endogenous nitric oxide inhibits neutrophil adherence to lung epithelial cells to modulate interleukin-8 release, LIFE SCI, 69(11), 2001, pp. 1333-1344
To investigate the effect of neutrophil adherence to epithelial cells on th
e release of interleukin 8 (IL-8), we measured neutrophil adherence in the
presence or absence of IFN-gamma +TNF-alpha +IL-1 beta (cytomix) stimulatio
n on cultured A549 epithelial cells. The extent of neutrophil adherence to
A549 epithelial cells was measured and the concomitant production of IL-8 a
nd nitrite were assayed. The roles of adhesion molecules and nitrite in mod
ulation of neutrophil adherence were examined by pretreatment with oversatu
rating ICAM-1 blocking antibody and L-NAME (1mM), respectively. There was a
time-dependent spontaneous and cytomix-induced release of IL-8 from epithe
lial cells, as well as a time-dependent increase in the magnitude of neutro
phil adherence to epithelial cells. Stimulation of epithelial cells with cy
tomix induced a further increase in neutrophil adherence. Pretreatment with
oversaturated ICAM-1 monoclonal antibody inhibited neutrophil adherence wi
th or without cytomix stimulation. The inhibition of neutrophil adherence t
o epithelial cells with ICAM-1 monoclonal antibody or a semipermeable membr
ane downregulated the release of IL-8 with or without cytomix stimulation.
Stimulation with cytomix decreased nitrite production. Both neutrophil adhe
rence and L-NAME pretreatment significantly inhibited the production of nit
rite. The inhibition of neutrophil adherence to epithelial cells with ICAM-
1 monoclonal antibody or a semipermeable membrane upregulated nitrite produ
ction. Pretreatment with L-NAME failed to modify the spontaneous release of
IL-8, but significantly enhanced the response to adherence and cytomix. In
conclusion, endogenous nitric oxide may play a role in preventing neutroph
il adherence to lung epithelial cells, thus modulating concomitant IL-8 rel
ease. (C) 2001 Elsevier Science Inc. All rights reserved.