Adhesion and motility of polymorphonuclear leukocytes isolated from the blood of rats exposed to ozone: potential biomarkers of toxicity.
Ozone (O3) exposure of rats results in airway epithelial injury and an infiltration of polymorphonuclear leukocytes (PMNs) into the lungs, suggesting alteration of PMN functions. To identify the altered PMN functions and their possible effects on epithelia, rats were exposed to air or 0.8 ppm O3 for 2 hr. PMNs were isolated from the blood and incubated with an epithelial cell line derived from rat lung (ARL-14) or primary alveolar type II cell cultures. The PMNs from the O3-exposed rats exhibited stimulated motility and spontaneous redistribution of actin filaments and adhered in a greater number to the epithelial cells when compared with the PMNs from the air-exposed rats. Actin caps usually formed at the sites of contact between the PMNs and epithelial cells, suggesting a cytoskeletal role in the inflammatory-epithelial cell interaction. By scanning electron microscopy, PMNs from air-exposed rats had features of non-motile cells. In a striking contrast to this, PMNs from O3-exposed rats revealed surface modifications, which were quite prominent at the sites of PMN-epithelial cell contacts. Despite these morphological changes, the PMNs from O3-exposed rats did not alter the epithelial resistance, a measure of paracellular permeability. In contrast to this, PMNs stimulated by phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine not only exhibited greater adhesion to the epithelial cells, but also caused a reduction in epithelial resistance. The changes reflecting altered morphology, motility, and adhesion of PMNs from O3-exposed rats may represent important steps in the O3-induced inflammatory response that precedes barrier disruption in vivo, but they are not associated with increased epithelial permeability in an in vitro system. Besides their mechanistic relevance, the alterations of vascular PMNs may serve as important biomarkers for detecting O3 effects.
Bhalla
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DK
Community and Environmental Medicine, University of California, Irvine 92717-1825.
Rasmussen
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RE
Daniels
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DS
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D015415:Biomarkers; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010126:Ozone