Association of plasminogen activators and matrix metalloproteinase-9 proteolytic cascade with blood-CNS barrier damage of angiostrongyliasis.
Blood-central nervous system (blood-CNS) barrier breakdown, an important pathophysiological event in meningitis, results in extravasation of leucocytes into subarachnoid space. The blood-CNS barrier disruption is mediated by primarily two enzyme systems, the plasminogen activators (PAs) and matrix metalloproteinases (MMPs). The present study showed that the activities of tissue-type PA (tPA), urokinase-type activator (uPA) and MMP-9 in cerebrospinal-like fluid (CSF-like fluid) were significantly increased in mice with eosinophilic meningitis compared with uninfected mice. Eosinophilia significantly correlated with tPA, uPA and MMP-9 activities, and albumin concentration. In addition, when GM6001, a specific matrix metalloproteinase blocker, was injected into infected mice, MMP-9 activity and total protein concentrations declined from their preinjection highs. These results suggest that the PAs and MMP-9 proteolytic cascade may be associated with blood-CNS barrier disruption in eosinophilic meningitis caused by Angiostrongylus cantonensis.
Chen
Ke-Min
KM
Department of Parasitology, Chung Shan Medical University, Taichung 402, Taiwan. kmc@csmu.edu.tw
Liu
Jer-Yuh
JY
Lai
Shih-Chan
SC
Hsu
Li-Sung
LS
Lee
Hsiu-Hsiung
HH
D000418:Albumins / Q000134:cerebrospinal fluid; D017185:Angiostrongylus cantonensis; D000818:Animals; D001798:Blood Proteins / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000293:injuries* / Q000382:microbiology; D004151:Dipeptides / Q000494:pharmacology; D004802:Eosinophilia / Q000097:blood / Q000134:cerebrospinal fluid / Q000382:microbiology; D004804:Eosinophils; D007958:Leukocyte Count; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D008581:Meningitis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010960:Plasminogen Activators / Q000134:cerebrospinal fluid*; D011480:Protease Inhibitors / Q000494:pharmacology; D017206:Strongylida Infections / Q000097:blood / Q000134:cerebrospinal fluid*; D010959:Tissue Plasminogen Activator / Q000134:cerebrospinal fluid; D014568:Urokinase-Type Plasminogen Activator / Q000134:cerebrospinal fluid
D000418:Albumins; D001798:Blood Proteins; D004151:Dipeptides; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9