Asbestos exposure induces MCP-1 secretion by pleural mesothelial cells.
We showed previously that both crocidolite and chrysotile asbestos inhalation induced a persistent macrophage inflammatory response within the pleural space of the rat. We postulated that the stimulus for pleural macrophage recruitment after asbestos exposure was the induction of monocyte chemoattractant protein-1 (MCP-1) synthesis by pleural mesothelial cells. To test this hypothesis, rat pleural mesothelial cells (RPMC) were cultured with or without chrysotile or crocidolite asbestos fibers (8 micrograms/cm2) in the presence (50 ng/mL) or absence of either tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). MCP-1 mRNA expression was assessed by RT-PCR in RPMC cultured for 2 to 24 hours, and MCP-1 protein secretion was measured by ELISA in conditioned medium from 24-hour and 48-hour cultures. Crocidolite and chrysotile fibers induced MCP-1 mRNA expression in RPMC which was maximal after 12 hours in the absence of cytokines, but which peaked after 2 hours when RPMC were challenged with asbestos + TNF-alpha or IL-1 beta. Both types of asbestos also significantly increased MCP-1 protein secretion after 24 and 48 hours (P < .0001), an effect that was potentiated by cytokine stimulation. Rats exposed by inhalation to either chrysotile or crocidolite asbestos fibers also had greater amounts of MCP-1 protein in their pleural lavage fluid than did sham-exposed rats. These findings suggest that MCP-1 secretion by RPMC may have a role in the initiation and/or potentiation of asbestos-induced pleural injury.
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
S
S
Tanaka
N
N
Choe
A
A
Iwagaki
D R
DR
Hemenway
E
E
Kagan
D000818:Animals; D001194:Asbestos / Q000494:pharmacology*; D017638:Asbestos, Crocidolite / Q000494:pharmacology; D017632:Asbestos, Serpentine / Q000494:pharmacology; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D019016:Mineral Fibers; D010994:Pleura / Q000737:chemistry / Q000166:cytology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D017632:Asbestos, Serpentine; D018932:Chemokine CCL2; D016207:Cytokines; D019016:Mineral Fibers; D012333:RNA, Messenger; D017638:Asbestos, Crocidolite; D001194:Asbestos