Lung injury induced by short-term intermittent trimellitic anhydride (TMA) inhalation.
We have developed a rat model of lung injury with interstitial pneumonitis, lung hemorrhage, and a systemic and pulmonary immune response to trimellitic anhydride (TMA)-haptenized proteins induced by TMA inhalation for 10 days. The present studies explored the induction of lung injury induced by short-term intermittent TMA inhalation, a model more likely to simulate short-term industrial exposures during inadvertent spills of TMA. Sprague-Dawley rats inhaled TMA powder (500 micrograms/m3) on days 1, 5, and 10, and were necropsied on day 30, 18 hours after a 6-hour TMA-inhalation challenge on day 29. Rats were bled every second day and at necropsy. Serum IgG, IgA, and IgM antibody to trimellityl rat serum albumin was measured by ELISA. There was a rise in IgM and IgA antibody to trimellityl rat serum albumin starting at day 5 that peaked at day 20 with a decline in IgM by day 30. IgG antibody rose at day 7, peaked at day 20, and plateaued. The IgG antibody level was 10 times higher than the IgA or IgM level. In a second experiment, 18 rats were administered TMA-inhalation exposure on days 1, 5, and 10, and a TMA challenge on day 22. The number of hemorrhagic foci, lung weights, and lung-displacement volumes at necropsy on day 23 were highly correlated with IgG, IgA, and IgM serum-antibody levels. In a final experiment, rats developed a mean of 112 hemorrhagic foci per lung on day 30 after receiving only two TMA-inhalation exposures on days 1 and 5 with a rechallenge on day 29. (ABSTRACT TRUNCATED AT 250 WORDS)
Zeiss
C R
CR
ACOS for Research and Development, VA Lakeside Medical Center, Chicago, IL 60611.
Leach
C L
CL
Levitz
D
D
Hatoum
N S
NS
Garvin
P J
PJ
Patterson
R
R
D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006470:Hemorrhage / Q000139:chemically induced / Q000276:immunology; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity*; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010795:Phthalic Acids; D010796:Phthalic Anhydrides; C015559:trimellitic anhydride