Response to Leydig cell apoptosis in the absence of testicular macrophages

Removal of apoptotic cells from the tissues appears to be a major function of resident tissue macrophages. In order to investigate further the role of testicular macrophages after massive Leydig cell death, adult rats were injected intra-testicularly with liposome-entrapped dichloromethylene diphosphonate (Cl2MDP-lp, right testis) to deplete testicular macrophages, and with NaCl (left testis) as control. Ten days later, the animals were injected intraperitoneally with ethylene dimethane sulphonate (EDS) to induce Leydig cell apoptosis. In macrophage-containing testes there was a 2-fold increase in the number of macrophages on days 1-3 after EDS treatment and Leydig cells were completely eliminated from the interstitium by the second day after treatment. The main differences in the response to Leydig cell death in macrophage-depleted testes were: (1) an early rise in the concentration of small mononuclear, lymphocyte-like cells, (2) a greater influx of circulating monocytes, (3) the existence of variable inflammatory infiltrates on days 3-4, and (4) the disappearance of infiltrating monocytes by day 10. These results suggest that resident macrophages prevent the inflammatory reaction elicited by massive Leydig cell death.