Cytokine regulation of complement receptor-mediated ingestion by mouse peritoneal macrophages. M-CSF and IL-4 activate phagocytosis by a common mechanism requiring autostimulation by IFN-beta.
Macrophage CSF (M-CSF, CSF-1) and IL-4 are two cytokines known to have effects on mature monocytic phagocytes in vitro. In this report we show that M-CSF and IL-4 activate resident mouse peritoneal macrophages to ingest particles via their C3b and C3bi receptors, which are not capable of mediating ingestion in resting cells. IgG-mediated ingestion was also increased by IL-4 and M-CSF. IL-1, IL-2, TNF-alpha, and IFN-gamma were not able to stimulate C receptor-mediated ingestion. Stimulation by IL-4 and M-CSF is dependent upon high cell density and greater than 24-h exposure to the cytokine. Interestingly, antibody to IFN-alpha/beta and mAb to IFN-beta inhibited the enhanced ingestion caused by both M-CSF and IL-4. However, neither IFN-alpha nor IFN-beta alone stimulated C receptor-mediated ingestion. M-CSF did not affect the ligand-independent distribution of CR3 on the macrophage surface. We conclude that two apparently unrelated cytokines, M-CSF and IL-4, both enhance macrophage phagocytosis of C and IgG-coated targets via a common pathway in which autocrine stimulation with IFN-alpha/beta is necessary but not sufficient.
Sampson
L L
LL
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Heuser
J
J
Brown
E J
EJ
D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D003179:Complement C3b / Q000502:physiology; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects*; D011951:Receptors, Complement / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D007370:Interferon Type I; D011951:Receptors, Complement; D011994:Recombinant Proteins; D015847:Interleukin-4; D003179:Complement C3b; D016173:Macrophage Colony-Stimulating Factor