Disruption of tissue plasminogen activator gene reduces macrophage migration.
Tissue plasminogen activator (tPA) is an essential component of the proteolytic cascade that lyses blood clots. Various studies also suggest that tPA plays important roles in peripheral nerve regeneration. Here we show that disruption of tPA gene reduces macrophage migration after sciatic nerve injury in mice. Moreover, lack of tPA activity attenuates migrating ability of macrophages and affects MMP-9 expression and activity in macrophages in vitro. Addition of ethylenediaminetetraacetic acid (EDTA), which inhibits MMPs, abolished the differences of migration ability of macrophages between tPA(+/+) and tPA(-/-) mice. Axonal regeneration is correlated with the increase of macrophage migration, suggesting that tPA may help create a beneficial environment for axonal regeneration through promoting macrophage infiltration. This study shows that tPA may play a role in nerve regeneration through regulating the migration ability of macrophages. This function of tPA may depend on, at least in part, upregulating MMP-9 expression and activity in macrophages.
Ling
Changchun
C
Department of Molecular Genetics and the Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, Shanghai 200032, PR China.
Zou
Tie
T
Hsiao
Yao
Y
Tao
Xianmei
X
Chen
Zu-Lin
ZL
Strickland
Sidney
S
Song
Houyan
H
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9