Macrophage apoptosis in rat skeletal muscle treated with bupivacaine hydrochloride: Possible role of MCP-1

The fate of macrophages infiltrating damaged rat skeletal muscle fibers after intramuscular injection of the anesthetic bupivacaine hydrochloride (BPVC) and the possible roles of monocyte chemoattractant protein-1 (MCP-1) were investigated. The number of macrophages reached a maximum level at 2 days after the injection and then gradually decreased. The number of apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was elevated at 2-4 days and decreased thereafter. In serial sections, TUNEL-positive cells were also immunopositive for RM-4, an antibody specific for identification of macrophages. Electron microscopy further confirmed that it was the macrophages themselves that were undergoing apoptosis. As assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), high levels of MCP-1 mRNA in BPVC-treated muscles were observed and positively correlated with maximum macrophage infiltration. However, the levels of MCP-1 mRNA returned to normal low values coincident with decrease of inflammation and healing of damaged muscle fiber. Local apoptosis of macrophages, under the control of MCP-1, may be involved in healing of BPVC-treated muscles.