Macrophageal/microglial cell activation and cerebral injury induced by excretory-secretory products secreted by Paragonimus westermani.
Cerebral paragonimiasis causes various neurological disorders including seizures, visual impairment and hemiplegia. The excretory-secretory product (ESP) released by Paragonimus westermani has a cysteine protease activity and plays important roles in its migration in the host tissue and modulation of host immune responses. To gain more insight into the pathogenesis of ESP in the brain, we investigated the inflammatory reaction and cerebral injury following microinjection of ESP into rat striatum. The size of injury was maximally observed 3 days after microinjection of ESP and then declined to control levels as astrocytes have repopulated the injury. ED1-positive monocytes and microglia were confluently found inside the injury. The mRNA expression of inducible nitric oxide synthase (iNOS) occurred as early as 9h after ESP injection and then declined to control levels within 1 day. The iNOS inhibitor aminoguanidine largely decreased the expression of iNOS but did not reduce the size of lesion caused by ESP. Interestingly, however, heat inactivation of ESP caused a decrease of injury formation with no altered expression of iNOS. The data indicate that ESP produces brain tissue injury by recruiting activated monocytes/microglia via heat-labile protease activity.
Lee
Jae-Chul
JC
Department of Pharmacology, College of Medicine, Ewha Women's Univeristy, Seoul, Republic of Korea.
Cho
Geum-Sil
GS
Kwon
Jae Hyun
JH
Shin
Myeong Heon
MH
Lim
Ji Hyae
JH
Kim
Won-Ki
WK
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006146:Guanidines / Q000494:pharmacology; D015801:Helminth Proteins / Q000737:chemistry / Q000494:pharmacology*; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009457:Neuroglia / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D009930:Organic Chemicals; D010238:Paragonimus / Q000737:chemistry*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004791:Enzyme Inhibitors; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006146:Guanidines; D015801:Helminth Proteins; D009930:Organic Chemicals; C435731:fluoro jade; D012313:RNA; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine