title: Suppression of splenic accessory cell function in mice exposed to gallium arsenide.
abstract: Acute exposure of mice to a single intratracheal dose of gallium arsenide (50, 100, and 200 mg/kg) depresses the primary IgM antibody response to the T-dependent antigen sheep red blood cells (SRBC) through alterations in the function of splenic accessory cells. To determine the mechanism by which GaAs exposure influences splenic accessory cells, the cells were isolated by adherence and their functional capability investigated 24 hr following GaAs exposure in the animal. Splenic adherent cells from GaAs-exposed mice were greatly impaired in their ability to process and present the particulate antigen SRBC to a SRBC-primed T-cell population. However, GaAs exposure did not inhibit phagocytosis of fluorescent covaspheres by these cells, nor did it inhibit in vivo phagocytosis of 51Cr-labeled SRBC, indicating that the findings reported here were not due to decreased uptake of antigen by the accessory cells. Furthermore, production of IL-1 by these cells from exposed mice was not different from control and addition of exogenous IL-1 to cultures did not reverse GaAs-induced inhibition of the primary antibody response. GaAs exposure did not affect the percentage of Ia positive macrophages (F4/80 positive cells), but the amount of cell surface IAk molecules expressed was significantly decreased as measured by flow cytometry. In contrast to the SRBC response, GaAs did not suppress the ability of adherent splenocytes to process and present the antigen pigeon cytochrome c to the helper/inducer T cell clone F1.A.2 or the antigen KLH (keyhole limpet hemocyanin) to KLH-primed T cells. Therefore, GaAs exposure interferes with the capacity of splenic macrophages to process and/or present the particulate antigen SRBC, but not the soluble protein antigens pigeon cytochrome c or KLH.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
authors.forename: E E
authors.initials: EE
authors.lastname: Sikorski
authors.forename: L A
authors.initials: LA
authors.lastname: Burns
authors.forename: K L
authors.initials: KL
authors.lastname: McCoy
authors.forename: M
authors.initials: M
authors.lastname: Stern
authors.forename: A E
authors.initials: AE
authors.lastname: Munson
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D001151:Arsenic / Q000008:administration & dosage / Q000633:toxicity*; D001152:Arsenicals; D002469:Cell Separation; D000939:Epitopes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005708:Gallium / Q000008:administration & dosage / Q000633:toxicity*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007375:Interleukin-1 / Q000032:analysis; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010587:Phagocytosis; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014132:Trachea
chemical_list: D001152:Arsenicals; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D007375:Interleukin-1; C043055:gallium arsenide; D005708:Gallium; D001151:Arsenic