Vb. Antony et al., PLEURAL MESOTHELIAL CELL EXPRESSION OF C-C (MONOCYTE CHEMOTACTIC PEPTIDE) AND C-X-C (INTERLEUKIN-8) CHEMOKINES, American journal of respiratory cell and molecular biology, 12(6), 1995, pp. 581-588
The arrival of inflammatory phagocytic cells, namely neutrophils and m
ononuclear phagocytes, in the pleural space is a hallmark of pleural i
nflammation. It is probable that the temporal arrival of cells is medi
ated via the release of chemotactic cytokines by activated mesothelial
cells. We hypothesized that human pleural mesothelial cells activated
by bacterial endotoxin lipopolysaccharide (LPS), interleukin-1 beta (
IL-1 beta), or tumor necrosis factor-alpha (TNF-alpha) release cell-sp
ecific chemokines from the C-C and C-X-C family of chemokines, specifi
cally monocyte chemoattractant protein 1 (MCP-1) and IL-8. We evaluate
d supernatants of stimulated mesothelial cells for biologic chemotacti
c activity for monocytes and neutrophils and quantitative antigenic pr
otein levels for MCP-1 and IL-8. Expression of the proteins at mRNA le
vel was tested via Northern blot analysis. We found that responses to
LPS were significantly higher (P < 0.05) than control supernatants of
unstimulated mesothelial cells. Responses to IL-1 beta and TNF-alpha w
ere significantly greater than those to LPS. Neutralization studies wi
th specific rabbit anti-MCP-l and IL-1 antibody demonstrated significa
nt decreases in bioactivity for MCP-1 and IL-8, indicating that mesoth
elial cell-derived MCP-1 and IL-8 play a significant role in the chemo
tactic activity seen in stimulated mesothelial cell supernatants. On s
pecific enzyme-linked immunosorbent assay testing, stimulated mesothel
ial cells produced significantly more MCP-1 and IL-8 when stimulated w
ith IL-1 beta or TNF-alpha as compared to LPS. mRNA expression for MCP
-1 peaked within 2 to 4 h following stimulation and was noted as early
as 1 h, LPS at 10 mu g/ml was a less potent stimulus than either IL-1
beta or TNF-alpha. We conclude that the mesothelial production of che
mokines MCP-1 and IL-8 plays an important role in the recruitment of m
onocytes and neutrophils to the pleural space, and the subsequent ampl
ification of the inflammatory process.