Increased neutrophil adherence to endothelial cells exposed to asbestos.
Inhalation of asbestos may activate the pulmonary endothelium to promote an inflammatory cell phenotype that participates in the development of pulmonary fibrosis. However, little is known about the effects of asbestos on endothelial cell function. Therefore, endothelial cells were exposed to chrysotile and crocidolite asbestos for up to 72 hr to investigate the effects of noncytotoxic concentrations of asbestos on cell function. Noncytolytic concentrations of chrysotile and crocidolite caused localized changes in cell morphology, resulting in activation of endothelial cells to a vacuolated, "spindle-shaped" morphology at sites of fiber deposition. The adherence of neutrophils (PMN) to control and asbestos-treated cultures was examined to determine the functional significance of this altered morphology. Chrysotile asbestos caused a time-dependent, 2- to 4-fold increase in PMN adherence that was localized to spindled endothelial cells in close contact with fibers. Monoclonal antibodies against intercellular adhesion molecule-1 (ICAM-1) inhibited this asbestos-induced PMN adherence. Solution hybridization demonstrated a 2.5-fold increase in steady-state levels of ICAM-1 mRNA in cells exposed to chrysotile asbestos for 8 hr. Exposure to crocidolite asbestos resulted in similar alteration in cell morphology and increase in PMN binding to endothelial cells, while a physically similar nonasbestos fiber, refractory ceramic fiber-1 did not cause morphologic change or increased PMN binding. These data suggest that asbestos fibers can specifically and directly activate endothelial cells, resulting in an activated cell morphology, increased ICAM-1 expression, and enhanced PMN adherence.
Treadwell
M D
MD
Department of Pharmacology and Toxicology, Dartmouth College Medical School, Hanover, New Hampshire 03755, USA.
Mossman
B T
BT
Barchowsky
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D001011:Aorta; D001194:Asbestos / Q000633:toxicity*; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine
D000911:Antibodies, Monoclonal; D002273:Carcinogens; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D001194:Asbestos