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Acquired
Immune Response as a Consequence of the Macrophage-Dependent Apoptotic Cell
Clearance and Role of the Monocyte Chemotactic S19 Ribosomal Protein Dimer
in This Connection |
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Arjun Shrestha,
Kei Horino, Hiroshi Nishiura, and Tetsuro Yamamoto |
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Division
of Molecular Pathology, Graduate School of Medical Sciences, Kumamoto University,
Kumamoto, Japan |
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SUMMARY: A connection between
the apoptotic cell clearance system and the acquired immune system was studied
in vivo. When fluorescence-labeled apoptotic HL-60 cells were inoculated
into footpads of guinea pigs and rabbits, monocyte/macrophage infiltration
rapidly occurred and subsequently the apoptotic cells as well as the macrophages
disappeared from the lesion by 48 hours without any macroscopical signs
of inflammation. Inversely, the fluorescent cell debris, which had been
engulfed by the macrophages, appeared and chronologically increased in the
draining lymphatics and the popliteal lymph nodes by 48 hours. Subsequently,
proliferation of T and B lymphocytes in the popliteal lymph nodes was observed.
Secondary inoculation of HL-60 cells in the flank skin of guinea pigs on
day 3 after the initial inoculation induced an acute immunologic dermatitis
with erythema, edema, vascular permeability enhancement, and polymorphonuclear
leukocyte infiltration. In vitro characterizations demonstrated the presence
of compliment dependent cytotoxic IgM antibody against HL-60 cells in their
sera. The infiltration of monocytes/macrophages at the apoptotic cell injection
site and the subsequent production of the anti-HL-60 cell IgM antibodies
were significantly suppressed by in situ injections of anti-S19 ribosomal
protein rabbit antibodies. These results indicated that the serial events
with the rapid apoptotic cell clearance by macrophages, the macrophage migration
to lymph nodes, and the antigen presentation to T lymphocytes by the macrophages
acquire immunity against apoptotic cells. It was also indicated that the
S19 ribosomal protein dimer was the major chemotactic factor in the initial
monocyte/macrophage infiltration to apoptotic cells. |
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