Am. J. Respir. Cell Mol. Biol., Vol 10, No. 3, Mar 1994, 245-252.
Interleukin-1-mediated release of interleukin-8 by asbestos-stimulated human pleural mesothelial cells
DE Griffith, EJ Miller, LD Gray, S Idell and AR Johnson
Department of Medicine, University of Texas Health Center, Tyler 75710.
The pleuropulmonary response to inhaled asbestos frequently involves
inflammation and release of various cytokines from lung cells. Among these,
interleukin-8 (IL-8) released from the mesothelium could augment
inflammation of the pleura by attracting neutrophils to the pleural space.
We used cultures of human pleural mesothelial cells (HPMC) to examine the
mechanism of IL-8 production by asbestos and cytokines. Suspensions of
amosite, chrysotile, or crocidolite asbestos in concentrations as low as 5
micrograms/ml enhanced release of IL-8 from HPMC during 6 h of incubation
at 37 degrees C. Electron microscopy of asbestos-treated HPMC showed that
the cells avidly engulfed each of the different types of asbestos fibers.
Two proinflammatory cytokines, interleukin-1 alpha (IL-1 alpha) and tumor
necrosis factor-alpha, enhanced IL-8 release within 2 h and had an even
greater effect after 6 h. Release of IL-8 was measured by an enzyme-linked
immunosorbent assay, and functional activity of the cytokine was assessed
by chemotaxis of human neutrophils. Identity of IL-8 in HPMC supernatants
was established by absorption with an antibody to IL-8. Preincubation of
HPMC with IL-1 receptor antagonist (IL-1ra) significantly decreased release
of IL-8 after stimulation with amosite or crocidolite asbestos. We conclude
that HPMC release IL-8 in response to asbestos stimulation and that the
response is, in part, mediated by IL-1, mainly in the form of IL-1 alpha.
