[Biological mechanism of macrophage activation by wear particles at the bone-implant interface]

To observe the response of membrane Ca(2+) channel of macrophage-like cells (MCs) to wear particles and analyze the cytoplasmic [Ca(2+)]i change in macrophage activation at the bone-implant interface.

The synoviocyte system of normal hip joint was established in vitro. Immunohistochemical technique (SABC) with CD68 Mab was used to differentiate MCs and fibroblast-like cells (FCs) in the system, and the time when MCs begin to perform phagocytosis was determined by SEM. 1.5 mg/ml (W/V) Ti alloy, Co-Cr alloy or UHMWPE particles suspension was added into the system to monitor the [Ca(2+)]i change in the MCs by confocal laser scanning microscope (CLSM).

Phagocytosis of MCs happened after 6 hours, but within 1 hour the Ca(2+) channel of their cell membrane opened for 1 - 6 times and caused rapid and transient pulses of [Ca(2+)]i in cytoplasm after different period of incubation. There was no significant difference between times or range of the [Ca(2+)]i pulse (P > 0.05). The group of UHMWPE particles had the longest incubation period (P < 0.05), but the interval of pulses was shorter than that in the group of Co-Cr alloy particles (P < 0.05). [Ca(2+)]i pulses still appeared when MCs were incubated by indomethecin (P > 0.05), but the phenomenon could be blocked by nimodipin.

Activation of macrophages at the bone-implant-interface could happen before they phagocytose wear particles. The primary switch-on mechanism of osteolysis mediated by cytokines at the bone-implant interface may be the opening of membrane Ca(2+) channel and pulse-like Ca(2+) influx of macrophages when stimulated by wear particles.