TY - JOUR
T1 - Brugia malayi asparaginyl-transfer RNA synthetase induces chemotaxis of human leukocytes and activates G-protein-coupled receptors CXCR1 and CXCR2
AU - Ramirez, Bernadette L.
AU - Howard, O. M.Zack
AU - Dong, Hui Fang
AU - Edamatsu, Takeo
AU - Gao, Ping
AU - Hartlein, Michael
AU - Kron, Michael
N1 - Funding Information:
Received 18 January 2005; accepted 9 November 2005; electronically published 6 March 2006. Potential conflicts of interest: none reported. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the US Government. Financial support: National Institutes of Health (contract CO-12400; grants TW-06625 and AI-53877). Reprints or correspondence: Dr. O. M. Zack Howard, PO Box B, 1050 Boyles St., Frederick, MD 21702 (howardz@ncifcrf.gov).
PY - 2006/4/15
Y1 - 2006/4/15
N2 - 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 rule 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 inflammatorymyopathies, 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 HRK-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.
AB - 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 rule 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 inflammatorymyopathies, 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 HRK-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.
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U2 - 10.1086/501369
DO - 10.1086/501369
M3 - Article
C2 - 16544258
AN - SCOPUS:33645783942
SN - 0022-1899
VL - 193
SP - 1164
EP - 1171
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 8
ER -