Identification, synthesis and immunogenicity of cuticular collagens from the filarial nematodes Brugia malayi and Brugia pahangi.
The major structural proteins of the cuticle of the filarial nematode parasites Brugia malayi and Brugia pahangi were identified by extrinsic iodination and sensitivity to clostridial collagenase. At least 16 acidic components were identified in adult worms by 2-dimensional electrophoresis, with molecular weights ranging from 35,000 to 160,000. These proteins appear to be cross-linked by disulphide bonds, and localised in the basal and inner cortical layers of the cuticle. The outer cortex, containing the epicuticle, is insoluble in 1% sodium dodecyl sulphate and 5% 2-mercaptoethanol, and can be isolated free of cellular material. Despite their inaccessibility to the immune system in intact worms, antibodies to the cuticular collagens are provoked in humans infected with a variety of filarial parasites. Immunological cross-reactivity was demonstrated between a 35 kDa component and human type IV (basement membrane) collagen. Autoantibodies to type IV collagen were detected in a number of individuals with lymphatic filariasis, although no correlation could be drawn with observed pathology. Synthesis of cuticular collagens is discontinuous, occurs at negligible levels in mature adult male worms, and does not appear to involve the production of small molecular weight precursors, in contrast to Caenorhabditis elegans. Hybridisation with a heterologous cDNA probe coding for the alpha 2 chain of chicken type 1 collagen suggests that they are encoded by a multigene family.
Selkirk
M E
ME
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, U.K.
Nielsen
L
L
Kelly
C
C
Partono
F
F
Sayers
G
G
Maizels
R M
RM
D000818:Animals; D000909:Antibodies, Helminth / Q000302:isolation & purification; D000947:Antigens, Helminth / Q000302:isolation & purification*; D001323:Autoantibodies / Q000302:isolation & purification; D002009:Brugia / Q000032:analysis*; D003094:Collagen / Q000096:biosynthesis / Q000276:immunology / Q000302:isolation & purification*; D015342:DNA Probes; D008565:Membrane Proteins / Q000302:isolation & purification*; D008854:Microscopy, Electron; D008970:Molecular Weight; D014158:Transcription, Genetic
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D001323:Autoantibodies; D015342:DNA Probes; D008565:Membrane Proteins; D003094:Collagen