1164 • JID 2006:193 (15 April) • Ramirez et al.
M A J O R A R T I C L E
Brugia malayi Asparaginyl–Transfer RNA Synthetase
Induces Chemotaxis of Human Leukocytes
and Activates G-Protein–Coupled Receptors CXCR1
Bernadette L. Ramirez,1O. M. Zack Howard,2Hui Fang Dong,3Takeo Edamatsu,2Ping Gao,2Michael Hartlein,4
and Michael Kron5
1Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines, Manila;
for Cancer Research, Laboratory of Molecular Immunoregulation, and
Program, National Cancer Institute-Frederick, Frederick, Maryland;
Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee
2National Cancer Institute, Center
3Science Applications International Corporation–Frederick Basic Research
4Institute Max von Laue, Paul Langevin, and
5Department of Medicine,
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
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) aspar-
aginyl-tRNA synthetase (AsnRS) is known to be an immunodominant antigen that induces strong human im-
munoglobulin G3 responses.
Recombinant B. malayi AsnRS was used to performcellularfunctionassays—forexample,chemotaxis
and kinase activation assays.
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
Our findings suggest that a filarial parasite chemoattractant protein may contribute to the de-
velopment of chronic inflammatory disease and that chemokine receptors may be therapeutic targets to ameliorate
Lymphatic filariasis is a chronic human parasitic disease in which the parasites repeatedlyprovoke
Lymphatic filariasis caused by Wuchereria bancrofti,Bru-
gia malayi, and Brugia timori is a complex human nem-
atode disease that affects 1200 million peopleworldwide
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
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 (firstname.lastname@example.org).
The Journal of Infectious Diseases
? 2006 by the Infectious Diseases Society of America. All rights reserved.
. B. malayi is found only in Asia, from India in the
west to Korea in the northeast and Indonesia in the
south, and infects ∼13 million people [1, 2]. The course
of infection with filarial parasites may last for decades
in the human host.
Filarial disease develops with the parasite repeated-
ly provoking host-derived acute, as well as long-term
chronic, inflammatory reactions within the lymphatic
channels and nodes, where the worms eventuallyreside
and reach sexual maturity . In Brugian filariasis, ep-
isodes of prolonged fever, adenolymphangitis,abscesses
of affected lymph nodes, and local residual scarring
occur frequently in infected persons . Withrecurrent
episodes of filarial lymphadenitis and complication of
secondary bacterial infection, progression to elephan-
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BmAsnRS Activates CXCR1 and CXCR2 • JID 2006:193 (15 April) • 1171
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