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.
Department of Orthopedic Surgery, Osaka Medical College, Takatsuki, Osaka, Japan.
Taisuke
T
Horiguchi
Masa-Aki
MA
Shibata
Yuko
Y
Ito
Nabil A S
NA
Eid
Muneaki
M
Abe
Yoshinori
Y
Otsuki
D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007273:Injections, Intramuscular; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000779:Anesthetics, Local; D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D002045:Bupivacaine