Macrophage Stimulation with Free Radical Release in the Early Stage of Lung Injury Due to Acute Toluene Diisocyanate Exposure

Details

• Personal Author:
  Banks DE ; Billie M ; Burrell R ; Castranova, Vincent ; Dedhia HV ; Doshi H ; Ma JYC ; Masri F ; Meisheri Y ; Pailes WH ; Vallyathan V
• Description:
  The role of pulmonary macrophages (AM) and free radical (FR) formation in acute toluene diisocyanate exposure (TD/) inhalation injury is unknown. The goal of our study was to characterize the inflammatory events leading to acute lung injury after a single sublethal, irritant dose of TD/. 21 rats were exposed to 1. 7 to 2 ppm of TD/ for 4 hours in an inhalation chamber. 10 rats served as a control on room air (Gr I). TD/ exposed rats were sacrificed at 1 (Gr II, n = 5), 20 (Gr III, n = 5) and 48 hours (Gr IV, n = 11) after exposure. Bronchoalveolar lavage (BAL) was analysed for total and differential cell count, cell viability, and lipid and protein content. AM function was assessed by chemiluminescence (CL) at rest and with zymosan stimulation (ZCL) in the absence or presence of the nitric oxide synthase inhibitor L-NAME. L-NAME dependent CL reflects nitric oxide synthase dependent activity (NOSCL). 02 based FR were measured by electron spin resonance technique using a PBN trap. Lungs were examined microscopically for quantification of severity of injury. No statistically significant differences in total cell counts, differential counts, viability, protein and lipid measurements, or lung histology were recognized among the 4 groups. ZCL increased 113% 20 hours after TD/ exposure but was not elevated 1 hour post-exposure. Likewise, NOSCL was significantly elevated by 630 % 20 hours post exposure. FR formation increased from 32 +/- 8 SEM (Gr I) to 55 +/- 4 (p<0.05) in Gr II to 70 +/- 8 SEM (p< 0.01) in Gr III. We conclude that the early lung response to an acute irritant TDI exposure is stimulation of AM as demonstrated by increased CL, induction of NOS and FR formation. This occurs before other measurable markers of acute lung injury. The relationship between this type of TDI-induced lung injury and the initiating mechanisms of TDI sensitization and TDI-induced asthma may be related but has not been addressed. [Description provided by NIOSH]
• Subjects:
  Animals Asthma Blood Environmental Exposure Free Radicals Isocyanates Laboratories Lipids Lung Macrophages Nitric Oxide Occupational Health Respiratory System Respiratory Tract Diseases Safety Toluene

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• Keywords:
  Bronchial Asthma Cell Function Cellular Effects Diisocyanates Exposure Levels Free Radicals Inhalation Injuries Laboratory Animals Nitric Oxide Proteins Pulmonary System

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• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  149
• NIOSHTIC Number:
  nn:20050916
• Citation:
  Am J Respir Crit Care Med 1994 Apr; 149(Abstract Issue):A849
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  1994
• Performing Organization:
  Center to Protect Workers' Rights
• Peer Reviewed:
  False
• Start Date:
  19900928
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Abstract Issue
• End Date:
  19970515
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:b98bdd435636504b235b81ab1d7563c696aa0d332757f05a51a4d8b788f09c44523bdf3d1f33f213a8603edc3552101fd5ff325b40fa2c52ec1704439606b7da
• Download URL:
  https://stacks.cdc.gov/view/cdc/211097/cdc_211097_DS1.pdf
• File Type:
  [PDF - 375.97 KB ]