Immunological and in-vivo neurological studies on a benzoic acid-specific T cell-derived antigen-binding molecule from the serum of a toluene-sensitive patient.
T-cell-derived antigen-binding molecules (TABMs) specific for benzoic acid were isolated from the serum of a toluene-sensitive patient. The resulting purified TABMs (BA-TABMs) did not contain immunoglobulin G and were associated with the cytokine transforming growth factor-beta (TGF-beta). BA-TABMs bound to benzoic acid conjugated to human serum albumin (BA-HSA), as well as to other chemicals conjugated to human serum albumin-including dinitrophenol and oxazolone. The binding of BA-TABMs to the conjugated chemicals increased the level of detectable TGF-beta, and a similar effect was observed with the unconjugated chemicals, benzoic acid and 2,4-dinitrophenol glycine. The increase in TGF-beta was critically dependent on the ratio between BA-TABMs and the conjugated or unconjugated chemicals; the increase was optimum at intermediate concentrations and absent at low and high concentrations. The authors used an established animal model in vivo and demonstrated that TGF-beta enhanced the inflammatory response induced by the release of neuropeptides from sensory nerves; this enhancement occurred in a dose-dependent manner. The BA-TABMs also enhanced this neurogenic inflammatory response in a dose-dependent manner, and this effect was blocked by anti-TGF-beta antibody. When the authors added either BA-HSA or benzoic acid, the effect of BA-TABMs on neurogenic inflammation was further enhanced at intermediate concentrations of antigen and was unaltered or reduced at higher concentrations. TABMs specific to particular chemicals, as a result of their association with cytokines (e.g., TGF-beta), may be implicated in symptom production in chemically sensitive patients.
Khalil
Z
Z
National Ageing Research Institute, University of Melbourne, Parkville, Australia.
Georgiou
G M
GM
Ogedegbe
H
H
Cone
R E
RE
Simpson
F
F
Little
C H
CH
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D019817:Benzoic Acid / Q000494:pharmacology*; D001665:Binding Sites; D004591:Electrophoresis, Polyacrylamide Gel; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000097:blood* / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis* / Q000276:immunology; D008297:Male; D009479:Neuropeptides / Q000096:biosynthesis / Q000187:drug effects*; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D011948:Receptors, Antigen, T-Cell / Q000097:blood*; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000502:physiology; D012867:Skin / Q000098:blood supply; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology; D014050:Toluene / Q000009:adverse effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D009479:Neuropeptides; D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta; D014050:Toluene; D019817:Benzoic Acid