title: Evidence of immunologic control of lung injury induced by trimellitic anhydride.
abstract: Trimellitic anhydride (TMA) is a chemical intermediate that has been shown to cause immunologically mediated respiratory syndromes in humans. We developed a rat model in which lung lesions accompanied by TMA-specific antibody resembled effects seen in humans. Two sets of experiments were undertaken to determine if TMA lung injury was primarily controlled by the immune system. Experiment 1: Rats were exposed to 95 micrograms/m3 of TMA 6 h/day, 5 days/wk for 2 wk during which time they received daily injections of either the immunosuppressant cyclophosphamide or saline. The TMA-exposed/saline control rats exhibited the usual TMA-induced lung lesions accompanied by TMA-specific antibody. However, the TMA-exposed/cyclophosphamide rats showed no lesions and no antibody. The spleen cells from all rats were subjected to lymphocyte blastogenesis assays using T- and B-cell mitogens. Results confirmed that cyclophosphamide-treated rats showed very little if any blastogenic response, whereas saline-treated rats gave the normal immune response. Thus, cyclophosphamide eliminated T- and B-cell function, which in turn prevented the occurrence of TMA lesions. Experiment 2: An initial passive transfer experiment showed that serum from TMA-sensitized rats could be adoptively transferred into naive recipient rats, which when given a single TMA inhalation challenge exhibited TMA-induced lesions. Similar attempts to transfer spleen cells or spleen cells plus serum did not predispose recipients for lesions. A second modified passive transfer of sensitized serum using a larger number of recipient rats, followed by a TMA challenge, resulted in lesions in 14 of the 16 rats.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: IIT Research Institute, Veterans Administration Lakeside Medical Center, Chicago, IL 60616.
authors.forename: C L
authors.initials: CL
authors.lastname: Leach
authors.forename: N S
authors.initials: NS
authors.lastname: Hatoum
authors.forename: H V
authors.initials: HV
authors.lastname: Ratajczak
authors.forename: C R
authors.initials: CR
authors.lastname: Zeiss
authors.forename: P J
authors.initials: PJ
authors.lastname: Garvin
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis; D003520:Cyclophosphamide / Q000494:pharmacology; D007116:Immunization, Passive; D007165:Immunosuppression Therapy; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity*; D010796:Phthalic Anhydrides / Q000276:immunology / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000906:Antibodies; D010795:Phthalic Acids; D010796:Phthalic Anhydrides; C015559:trimellitic anhydride; D003520:Cyclophosphamide