Endotoxin potentiates ozone-induced pulmonary chemokine and inflammatory responses.
Urban air consists of a combination of environmental pollutants. Recent studies have suggested that normally innocuous doses of a particular pollutant may be rendered more toxic to the lung if primed by earlier events. Pulmonary inflammation has been observed in humans and in many animal species after endotoxin and ozone exposures. The present study was designed to test the hypothesis that inhalation of low levels of endotoxin following ozone exposure will potentiate ozone-induced lung injury. We exposed 8-week-old C57BL/6J mice to 1 ppm ozone for 24 hours; inhalation of low-dose endotoxin (37.5 EU) for 10 minutes; or 1 ppm ozone immediately followed by endotoxin inhalation (37.5 EU). The mice were examined 4 or 24 hours post exposure. After 24 hours of recovery, significant increases were measured in bronchoalveolar lavage (BAL) fluid levels of protein and lavageable polymorphonuclear neutrophils (PMNs) after coexposure to ozone followed immediately by endotoxin inhalation as compared to exposures individually. Messages encoding macrophage inflammatory protein (MIP)-1beta, MIP-1alpha, MIP-2, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1alpha, IL-1beta, IL-1Ra, IL-6, and Macrophage Migration Inhibitory Factor (MIF) were significantly elevated 24 hours post ozone followed by endotoxin as compared to exposure to ozone or endotoxin individually. These results demonstrate that preexposure to ozone, which primarily attacks the epithelium, can cause sensitization to a secondary stimulus through a mechanism that culminates in a greater and prolonged onset of inflammatory cell recruitment, pulmonary edema, and increased expression of chemokine and cytokine messages.
Johnston
Carl J
CJ
Department of Environmental Medicine, University of Rochester, New York 14642, USA.
Oberdörster
Günter
G
Gelein
Robert
R
Finkelstein
Jacob N
JN
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology; D010083:Oxidants, Photochemical / Q000494:pharmacology*; D010126:Ozone / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced*; D012333:RNA, Messenger / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines; D004731:Endotoxins; D010083:Oxidants, Photochemical; D012333:RNA, Messenger; D010126:Ozone