Cytotoxicity in feline leukemia virus subgroup-C infected fibroblasts is mediated by adherent bone marrow mononuclear cells.
The pathogenesis of retrovirus-induced erythroid aplasia in cats is unknown. In studies to define mechanisms of cytotoxicity associated with retroviral infections, bone marrow mononuclear cells (BMMC) from healthy specific pathogen-free cats were co-cultured with uninfected feline embryonic fibroblasts (FEA cells) and FEA cells infected with feline leukemia virus (FeLV) of subgroup A (FEA-A) or subgroup C (FEA-C). Moderate to marked cytotoxicity (CPE) developed in co-cultures of BMMC and FEA-C cells on Days 5 to 7 of incubation but not in co-cultures of BMMC and FEA-A or BMMC and uninfected cells (FEA-CT). Cytotoxicity was associated with adherent cells of light density (1.056) from bone marrow and peripheral blood, which were positive for alpha naphthyl butyrate esterase activity. Stimulation of adherent cells with phorbol ester or addition of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) caused similar CPE in FEA-CT cells. The TNF-alpha concentrations in the culture supernatants of BMMC+FEA-C were higher than those of BMMC+FEA-A or BMMC+FEA-CT, and addition of anti-TNF antibodies to the cultures blocked the CPE. These data support the hypothesis that macrophages exposed to FeLV-C cause CPE in co-cultures of BMMC and FEA cells by a mechanism involving TNF-alpha. It is suggested that TNF-alpha may be involved in the suppression of hematopoiesis in cats which develop FeLV-C induced erythroid aplasia.
Khan
K N
KN
Department of Veterinary Pathobiology, College of Veterinary Medicine, Ohio State University, Columbus 43210.
Kociba
G J
GJ
Wellman
M L
ML
Reiter
J A
JA
D000818:Animals; D000906:Antibodies; D001854:Bone Marrow Cells; D002265:Carboxylic Ester Hydrolases / Q000032:analysis; D002415:Cats; D002448:Cell Adhesion; D016207:Cytokines / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000382:microbiology*; D005256:Leukemia Virus, Feline / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D000906:Antibodies; D016207:Cytokines; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002265:Carboxylic Ester Hydrolases; C021855:naphthylbutyrate esterase