Macrophages are involved in hexachlorobenzene-induced adverse immune effects.
Hexachlorobenzene (HCB) is a persistent environmental pollutant that causes adverse immune effects in man and rat. The Brown Norway (BN) rat is very susceptible to HCB-induced immunopathology and oral exposure causes inflammatory skin and lung lesions, splenomegaly, lymph node (LN) enlargement, and increased serum levels of IgE and anti-ssDNA IgM. T cells play an important role but do not account for all adverse effects induced by HCB. Macrophages are probably also important and the relationship between macrophages and T cells was further investigated. To eliminate macrophages clodronate-liposomes were used. Furthermore, a kinetic study was performed to obtain insight in the early phase of the HCB-induced immune response. Also, experiments were performed to detect specific memory T cells. Therefore, an adoptive transfer study was performed. Our results indicate that macrophages are indeed involved in HCB-induced skin lesions, lung eosinophilia, and elevation of IgM against ssDNA. Kinetics showed that both skin and lung lesions appeared early after exposure. Moreover, immune effects could not be adaptively transferred. Thus, both macrophages and T cells are involved in HCB-induced immune effects but HCB exposure does not lead to specific T cell sensitization. Presumably, HCB exposure induces macrophage activation, thereby generating adjuvant signals that polyclonally stimulate T cells. Together, these events may lead to the observed immunopathology in BN rats.
Ezendam
Janine
J
National Institute for Public Health and the Environment, Laboratory for Toxicology, Pathology and Genetics, Bilthoven, PO Box 1 3720 BA, The Netherlands. Janine.Ezendam@rivm.nl
Kosterman
Kevin
K
Spijkerboer
Henneke
H
Bleumink
Rob
R
Hassing
Ine
I
van Rooijen
Nico
N
Vos
Joseph G
JG
Pieters
Raymond
R
D018712:Analgesics, Non-Narcotic; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D002460:Cell Line; D004002:Clodronic Acid; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006581:Hexachlorobenzene / Q000633:toxicity*; D007075:Immunoglobulin M / Q000032:analysis; D016219:Immunotherapy, Adoptive; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D012867:Skin / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015430:Weight Gain / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D004277:DNA, Single-Stranded; D007075:Immunoglobulin M; D004002:Clodronic Acid; D006581:Hexachlorobenzene