title: Ym1, an eosinophilic chemotactic factor, participates in the brain inflammation induced by Angiostrongylus cantonensis in mice.
abstract: Angiostrongylus cantonensis is an emerging zoonotic pathogen that has caused hundreds of cases of human angiostrongyliasis worldwide. The larva in nonpermissive hosts cannot develop into an adult worm and can cause eosinophilic meningitis and ocular angiostrongyliasis. The mechanism of brain inflammation caused by the worm remains poorly defined. According to previous data of GeneChip, Ym1 in the brain of mice 21 days after infection with A. cantonensis was highly upregulated to over 7,300 times than the untreated mice. Ym1 is an eosinophilic chemotactic factor with the alternative names of chitinase-3-like protein 3, eosinophil chemotactic cytokine, and ECF-L. Ym1 displays chemotactic activity for T lymphocytes, bone marrow cells, and eosinophils and may favor inflammatory responses induced by parasitic infections and allergy. It has been reported that Ym1 is synthesized and secreted by activated macrophages during parasitic infection (Chang et al., J Biol Chem 276(20):17497-17506, 2001). In the brain, microglia are alternatively activated macrophage-derived cells which are the key immune cells in central nervous system inflammation. To explore the role of Ym1 in inflammation caused by A. cantonensis-infected mice, we examined the levels of Ym1 in the sera and cerebrospinal fluid (CSF) of the infected animals, followed by detection of the mRNA expression level of Ym1 in various organs including the brain, lung, liver, spleen, and kidney and of the cytokines IL-5 and IL-13 in the brain of the infected mice with or without intraperitoneal injection of minocycline (an inhibitor of microglial activation) by real-time reserve transcription PCR. Furthermore, immunolocalization of Ym1 in the brains of the infected mice was observed by using a fluorescence microscope. Our results showed that Ym1 was most highly expressed in the brains and CSF of the infected mice along with the process of inflammation. The antibody localized Ym1 to the microglia in the brain of the mice in both infection and minocycline + infection groups. And as in the brain, the mRNA level of Ym1 changed more obviously than IL-5 and IL-13. The study implies that Ym1 might serve as an alternative potential pathological marker which is detected not only in the sera and CSF but also in the brains of the infected mice and Ym1 secreted by microglia might be involved in eosinophilic meningitis and meningoencephalitis caused by A. cantonensis infection.
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou 510080 Guangdong Province, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.forename: Zhiyue
authors.initials: Z
authors.lastname: Lv
authors.forename: Fuzhen
authors.initials: F
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
authors.forename: Qixian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shuting
authors.initials: S
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Zeng
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wu
authors.forename: Zhongdao
authors.initials: Z
authors.lastname: Wu
mesh_terms: D017185:Angiostrongylus cantonensis / Q000276:immunology* / Q000472:pathogenicity*; D000825:Animal Structures / Q000473:pathology; D000818:Animals; D002555:Cerebrospinal Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D018793:Interleukin-13 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D037102:Lectins / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044967:Serum / Q000737:chemistry; D017206:Strongylida Infections / Q000469:parasitology / Q000473:pathology; D001619:beta-N-Acetylhexosaminidases / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D037102:Lectins; C429541:Chil3 protein, mouse; D001619:beta-N-Acetylhexosaminidases