Tingible body macrophages, characterized by CD68+ F4/80-, in spleen and lymph node express significant level of MFG-E8. Peritoneal macrophages elicited by thioglycollate secrete abundant MFG-E8 protein of 74 kD in the culture supernatant. The macrophages from MFG-E8(-/-) mice engulf few apoptotic cells compared to the macrophages from their normal littermates in vitro. Addition of recombinant MFG-E8 in the culture restored the ability of MFG-E8(-/-) Mφs to engulf apoptotic cells in a doze-dependent manner.