Blockade of Macrophage Colony‐Stimulating Factor Reduces Macrophage Proliferation and Accumulation in Renal Allograft Rejection

Macrophage accumulation within an acutely rejecting allograft occurs by recruitment and local proliferation. To determine the importance of M‐CSF in driving macrophage proliferation during acute rejection, we blocked the M‐CSF receptor, c‐fms, in a mouse model of acute renal allograft rejection. C57BL/6 mouse kidneys (allografts, n = 20) or BALB/c kidneys (isografts, n = 5) were transplanted into BALB/c mice. Anti‐c‐fms antibody (AFS98) or control Ig (50 mg/kg/day, i.p.) was given daily to allografts from days 0–5. All mice were killed day 6 postoperatively. Expression of the M‐CSF receptor, c‐fms, was restricted to infiltrating CD68+ macrophages. Blockade of c‐fms reduced proliferating (CD68+/BrdU+) macrophages by 82% (1.1 v 6.2%, p