Radiation leukemia virus (RadLV)-induced leukemogenesis is associated with an increased number and activity of thymic macrophages.
The radiation leukemia virus (RadLV) is a chronic leukemia retrovirus that induces thymic lymphomas in C57BL/6 mice after a latency of 3 to 6 months. During the pre-leukemic (PL) period, the number of thymic macrophages gradually increased up to 100 fold. Of the cells in a RadLV-induced lymphoma, 0.3% were large macrophages packed with infected lymphoma cells. These thymic lymphoma macrophages (TLM) also ingested RadLV-induced lymphoma cells in vitro. Cultured RadLV-induced lymphoma lines could activate and fix C3 fragments through the alternative complement pathway (ACP). C3-bound lymphoma cells elicited an oxidative burst (OB) response in TLM but not in bone-marrow macrophages (BMM). However, IL4 treatment of BMM rendered them capable of responding with an OB following triggering by C3-opsonized cells. Thymic macrophages (TM) responded moderately with OB to C3-opsonized cells and this response was elevated if the TMs were treated by rIL4. The OB reaction of the TLMs could be partially inhibited by anti-LFA-I or anti-MALA-2 antibodies, and was completely inhibited by anti-CR3 antibodies. These results suggest that IL4 can prime macrophages for triggering an OB reaction and that the interaction between C3-opsonized cells and IL4-primed macrophages is mediated primarily through CR3.
Messika
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E
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Gallily
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R
Yefenof
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E
D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003176:Complement C3 / Q000032:analysis; D003170:Complement Pathway, Alternative; D015847:Interleukin-4 / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000472:pathogenicity*; D008223:Lymphoma / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D011289:Preleukemia / Q000382:microbiology* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013945:Thymoma / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D013950:Thymus Gland / Q000166:cytology / Q000473:pathology*; D013953:Thymus Neoplasms / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology
D003176:Complement C3; D011994:Recombinant Proteins; D015847:Interleukin-4