Airway epithelial damage and release of inflammatory mediators in human lung parenchyma after sulfur mustard exposure.
This study was performed to evaluate the morphological effects of sulfur mustard on human lung parenchyma in vitro and to measure the metabolites of arachidonic acid which are released during acute exposure to the alkylating agent. Histological analysis of the tissue following exposure to sulfur mustard for a period of 45 min at 10 mM revealed the presence of paranuclear vacuoles in the epithelium, specifically, in the ciliated cells. The release of metabolites of arachidonic acid were determined in the bath fluids by an enzymo-immunoassay. The basal release of prostaglandin E2 (PGE2: 1.36 +/- 0.33 ng/g tissue) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha: 8.83 +/- 1.17 ng/g tissue) were not modified during tissue exposure to sulfur mustard (45 min, 0.1 mM). In addition, the basal release of cysteinyl-leukotriene E4 (LTE4: 1.55 +/- 0.44 ng/g tissue) was also not altered by challenge of the tissues with sulfur mustard. In contrast, when the human lung parenchyma was stimulated with anti human IgE (anti-IgE) only the basal release of the metabolite of the 5-lipoxygenase pathway was significantly increased (LTE4: 6.84 +/- 1.57 ng/g tissue). These data suggest that sulfur mustard may produce morphological alterations in epithelial cells and at the time point studied (45 min exposure), this effect is not associated with a release of arachidonic acid metabolites. However, the increased release of LTE4 by anti-IgE suggests that the target cells for sulfur mustard and anti-IgE in the human lung may be different.
Calvet
J H
JH
Laboratoire de Toxicologie Respiratoire, Centre d'Etudes du Bouchet (Defense Medical Research Center), Vert-Le-Petit, France.
Gascard
J P
JP
Delamanche
S
S
Brink
C
C
D000477:Alkylating Agents / Q000633:toxicity*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E / Q000494:pharmacology; D066298:In Vitro Techniques; D017999:Leukotriene E4 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008853:Microscopy; D009151:Mustard Gas / Q000633:toxicity*; D011453:Prostaglandins / Q000378:metabolism*; D013997:Time Factors
D000477:Alkylating Agents; D011453:Prostaglandins; D016718:Arachidonic Acid; D007073:Immunoglobulin E; D017999:Leukotriene E4; D001094:Arachidonate 5-Lipoxygenase; D009151:Mustard Gas