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Brugia malayi asparaginyl-transfer RNA synthetase induces chemotaxis of human leukocytes and activates G-protein-coupled receptors CXCR1 and CXCR2. J Infect Dis 2006 Apr 15;193(8):1164-71

Date

03/18/2006

Pubmed ID

16544258

DOI

10.1086/501369

Abstract

Background. Lymphatic filariasis is a chronic human parasitic disease in which the parasites repeatedly provoke acute and chronic inflammatory reactions in the host bloodstream and lymphatics. Excretory-secretory products derived from filariae are believed to play an important role in the development of associated immunologic conditions; however, the specific mechanisms involved in these changes are not well understood. Recently, human cytoplasmic aminoacyl-transfer (t) RNA synthetases, which are autoantigens in idiopathic inflammatory myopathies, were shown to activate chemokine receptors on T lymphocytes, monocytes, and immature dendritic cells by recruiting immune cells that could induce innate and adaptive immune responses. Filarial (Brugia malayi) asparaginyl-tRNA synthetase (AsnRS) is known to be an immunodominant antigen that induces strong human immunoglobulin G3 responses.Methods. Recombinant B. malayi AsnRS was used to perform cellular function assays--for example, chemotaxis and kinase activation assays.Results. Unlike human AsnRS, parasite AsnRS is chemotactic for neutrophils and eosinophils. Recombinant B. malayi AsnRS but not recombinant human AsnRS induced chemotaxis of CXCR1 and CXCR2 single-receptor-transfected HEK-293 cell lines, blocked CXCL1-induced calcium flux, and induced mitogen-activated protein kinase.Conclusions. Our findings suggest that a filarial parasite chemoattractant protein may contribute to the development of chronic inflammatory disease and that chemokine receptors may be therapeutic targets to ameliorate parasite-induced pathology.

Author List

Ramirez BL, Howard OM, Dong HF, Edamatsu T, Gao P, Hartlein M, Kron M

Author

Michael Kron MD Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antibodies, Helminth
Aspartate-tRNA Ligase
Brugia malayi
Calcium
Cell Line
Chemotaxis, Leukocyte
Filariasis
GTP-Binding Proteins
Humans
Mitogen-Activated Protein Kinase Kinases
Neutrophils
Pertussis Toxin
Protein Structure, Tertiary
RNA, Transfer, Amino Acyl
Receptors, Interleukin-8A
Receptors, Interleukin-8B
Recombinant Proteins
jenkins-FCD Prod-410 e9586552fe7f53c71f7923aa6e27aeabbd3c2473