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Distribution and inducibility of a P450I activity in cellular components of the avian immune system

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Abstract

The level of expression of the cytochrome P450 system in an immune tissue could influence the sensitivity of that immune tissue to damage by xenobiotics. The capacity of immune organs and their cellular components for P450I-catalyzed metabolism was assayed in the 4-week-old chicken using the P450I-specific ethoxyresorufin-O-deethylase (EROD) assay and the P450I-inducer, 3,4,3′,4′-tetrachlorobiphenyl (TCB). After induction by TCB, EROD was detectable in microsomes from whole thymus, bursa and in peritoneal exudate cells (containing primarily macrophages) at levels of 28.3, 7.2 and 1.3 pmol/mg microsomal protein/min, respectively; the level in control liver was 89.9 pmol/mg microsomal protein/min. No activity was detected in these immune tissues without induction. The P450I specific in vitro inhibitor, α-naphthoflavone (NF) inhibited the TCB-induced liver and immune tissue EROD by 50% at concentrations in the range of 0.07–0.1 μM. The cellular distribution of EROD in the bursa and thymus was studied in lymphocytes and supporting tissue cells after their separation by density gradient centrifugation. Much higher TCB-induced EROD was detected in immune tissue supporting cells than in lymphocytes, particularly in the thymus. The P450I in the supporting tissue of the bursa and thymus at 1 week post-hatch was also measured after eradication of the lymphocytes in both immune tissues by in ovo administration of CP. TCB-induced EROD was 12-fold higher in the lymphocyte-depleted thymus than in normal thymus, with a less marked but similar pattern in the bursa. These studies suggest that after exposure to a P450I inducer, levels of P450I are much higher in the supporting cells of immune organs than in the immune cells themselves.

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Abbreviations

CP:

cyclophosphamide

TCDD:

2,3,7,8-tetrachlorodiben-zodioxin

TCB:

3,4,3′,4′-tetrachlorobiphenyl

EROD:

ethoxyresorufin-O-deethylase

NF:

α-naphthoflavone

PB:

sodium phenobarbital

BCA:

bicinchoninic acid

PECs:

peritoneal exudate cells

i. p.:

intraperitoneal

b.w.:

body weight

PBS:

phosphate buffered saline

DI:

days of incubation

WPH:

weeks posthatch

DPH:

days posthatch

BZOD:

benzyloxy-phenoxazone-o-debenzylase

IC50 :

50% inhibitory concentration

DMSO:

dimethylsulfoxide

BP:

benzo(a)pyrene

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Authors and Affiliations

  1. Dept. Avian & Aquatic Animal Medicine, Cornell University, 203 Rice Hall, 14853, Ithaca, NY, USA

    Nancy A. Lorr, Richelle A. Hemendinger & Stephen E. Bloom

  2. Department of Microbiology, Immunology, and Parasitology, Cornell University, Ithaca, New York, USA

    Karen A. Golemboski & Rodney R. Dietert

  3. Institute for Comparative and Environmental Toxicology, Cornell University, Ithaca, New York, USA

    Nancy A. Lorr, Karen A. Golemboski, Rodney R. Dietert & Stephen E. Bloom

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  1. Nancy A. Lorr
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  3. Richelle A. Hemendinger
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  4. Rodney R. Dietert
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  5. Stephen E. Bloom
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Lorr, N.A., Golemboski, K.A., Hemendinger, R.A. et al. Distribution and inducibility of a P450I activity in cellular components of the avian immune system. Arch Toxicol 66, 560–566 (1992). https://doi.org/10.1007/BF01973386

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  • DOI: https://doi.org/10.1007/BF01973386

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