|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 94 No. 4 (August 15), 1999:
pp. 1418-1428
A Novel Serpin Expressed by Blood-Borne Microfilariae of the Parasitic
Nematode Brugia malayi Inhibits Human Neutrophil Serine
Proteinases
Xingxing Zang,
Maria Yazdanbakhsh,
Haobo Jiang,
Michael R. Kanost, and
Rick M. Maizels
From the Institute of Cell, Animal and Population Biology, University
of Edinburgh, Edinburgh, UK; the Department of Parasitology, Leiden
University Medical Center, Leiden, The Netherlands; and the Department
of Biochemistry, Kansas State University, Manhattan, KS.
Serine proteinase inhibitors (serpins) play a vital regulatory role
in a wide range of biological processes, and serpins from viruses have
been implicated in pathogen evasion of the host defence system. For the
first time, we report a functional serpin gene from nematodes that may
function in this manner. This gene, named Bm-spn-2, has been
isolated from the filarial nematode Brugia malayi, a causative
agent of human lymphatic filariasis. Polymerase chain reaction (PCR)
and Western blot experiments indicate that Bm-spn-2 is
expressed only by microfilariae (Mf), which are the long-lived
blood-dwelling larval stage. A survey of the greater than 14,000 expressed sequence tags (ESTs) from B malayi deposited in dbEST
shows that greater than 2% of the ESTs sequenced from Mf cDNA
libraries correspond to Bm-spn-2. Despite its abundance in the
microfilarial stage, Bm-spn-2 has not been found in any other
point in the life cycle. The predicted protein encoded by Bm-spn-2 contains 428 amino acids with a putative signal
peptide. Antibodies to recombinant Bm-SPN-2 protein react specifically with a 47.5-kD native protein in Mf extract. Bm-SPN-2 is one of the
largest of the 93 known serpins, due to a 22 amino acid
carboxy-terminal extension, and contains the conserved serpin signature
sequence. Outside these regions, levels of homology are low, and only a distant relationship can been seen to a Caenorhabditis elegans serpin. The Bm-spn-2 gene contains 6 introns, 2 of which appear to be shared by both nematode species. The B malayi introns
have an extended and conserved 3' splice site and are relatively
large compared with C elegans. A panel of mammalian serine
proteinases were screened and Bm-SPN-2 protein was found to
specifically inhibit enzymatic activity of human neutrophil cathepsin G
and human neutrophil elastase, but not a range of other serine
proteinases. It is possible that Bm-SPN-2 could function as a
stage-specific serpin in the blood environment of the microfilarial
parasite in protection from human immunity and thus may be a good
candidate for protective vaccine.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. C. Pak, V. Kumar, C. Tsu, C. J. Luke, Y. S. Askew, D. J. Askew, D. R. Mills, D. Bromme, and G. A. Silverman
SRP-2 Is a Cross-class Inhibitor That Participates in Postembryonic Development of the Nematode Caenorhabditis elegans: INITIAL CHARACTERIZATION OF THE CLADE L SERPINS
J. Biol. Chem.,
April 9, 2004;
279(15):
15448 - 15459.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Schierack, R. Lucius, B. Sonnenburg, K. Schilling, and S. Hartmann
Parasite-Specific Immunomodulatory Functions of Filarial Cystatin
Infect. Immun.,
May 1, 2003;
71(5):
2422 - 2429.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zang, P. Taylor, J. M. Wang, D. J. Meyer, A. L. Scott, M. D. Walkinshaw, and R. M. Maizels
Homologues of Human Macrophage Migration Inhibitory Factor from a Parasitic Nematode. GENE CLONING, PROTEIN ACTIVITY, AND CRYSTAL STRUCTURE
J. Biol. Chem.,
November 8, 2002;
277(46):
44261 - 44267.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. MacDonald, M. I. Araujo, and E. J. Pearce
Immunology of Parasitic Helminth Infections
Infect. Immun.,
February 1, 2002;
70(2):
427 - 433.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Loukas and P. Prociv
Immune Responses in Hookworm Infections
Clin. Microbiol. Rev.,
October 1, 2001;
14(4):
689 - 703.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. R. Atchley, T. Lokot, K. Wollenberg, A. Dress, and H. Ragg
Phylogenetic Analyses of Amino Acid Variation in the Serpin Proteins
Mol. Biol. Evol.,
August 1, 2001;
18(8):
1502 - 1511.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zang, A. K. Atmadja, P. Gray, J. E. Allen, C. A. Gray, R. A. Lawrence, M. Yazdanbakhsh, and R. M. Maizels
The Serpin Secreted by Brugia malayi Microfilariae, Bm-SPN-2, Elicits Strong, but Short-Lived, Immune Responses in Mice and Humans
J. Immunol.,
November 1, 2000;
165(9):
5161 - 5169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. F. Gregory, A. K. Atmadja, J. E. Allen, and R. M. Maizels
The Abundant Larval Transcript-1 and -2 Genes of Brugia malayi Encode Stage-Specific Candidate Vaccine Antigens for Filariasis
Infect. Immun.,
July 1, 2000;
68(7):
4174 - 4179.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Lizotte-Waniewski, W. Tawe, D. B. Guiliano, W. Lu, J. Liu, S. A. Williams, and S. Lustigman
Identification of Potential Vaccine and Drug Target Candidates by Expressed Sequence Tag Analysis and Immunoscreening of Onchocerca volvulus Larval cDNA Libraries
Infect. Immun.,
June 1, 2000;
68(6):
3491 - 3501.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Loukas, M. Hintz, D. Linder, N. P. Mullin, J. Parkinson, K. K. A. Tetteh, and R. M. Maizels
A Family of Secreted Mucins from the Parasitic Nematode Toxocara canis Bears Diverse Mucin Domains but Shares Similar Flanking Six-cysteine Repeat Motifs
J. Biol. Chem.,
December 8, 2000;
275(50):
39600 - 39607.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
