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Variable degree of alternative complement pathway-mediated hemolysis in Indian visceral leishmaniasis induced by differential expression of 9-O-acetylated sialoglycans.

AbstractBACKGROUND:
Increased expression of linkage-specific 9-O-acetylated sialoglycans (9-O-AcSGs) has been demonstrated on erythrocytes from patients with visceral leishmaniasis (VL) by use of Achatinin-H. We assessed the capacity of this glycotope to influence hemolysis via activation of the alternative complement pathway in patients with VL, compared with that in healthy control subjects.
METHODS:
The differential expression of 9-O-AcSGs on surfaces of erythrocytes was measured, 9-O-AcSGs were affinity purified, and the molecular determinants were identified by Western blotting. The degree of alternative complement pathway-mediated hemolysis was compared with expression of 9-O-AcSGs on erythrocytes.
RESULTS:
Enhanced expression of linkage-specific 9-O-AcSGs was demonstrated on erythrocytes from patients with active VL. Six distinct molecular determinants present only on diseased erythrocytes were affinity purified and were absent after elimination of parasite burden. A correlation (r2=0.9) was observed between the presence of 9-O-AcSGs and the degree of alternative complement pathway-mediated hemolysis.
CONCLUSION:
The 9-O-AcSGs expressed on erythrocytes from patients with VL are potent complement activators, causing enhanced hemolysis via activation of the alternative complement pathway, and may account for the anemia that is a common manifestation of VL.
AuthorsAnil Kumar Chava, Mitali Chatterjee, Vineeta Sharma, Shyam Sundar, Chitra Mandal
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 189 Issue 7 Pg. 1257-64 (Apr 01 2004) ISSN: 0022-1899 [Print] United States
PMID15031795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Lectins
  • Polysaccharides
  • Sialic Acids
  • achatinin(H)
  • 9-O-acetyl-N-acetylneuraminic acid
Topics
  • Adolescent
  • Adult
  • Animals
  • Blotting, Western
  • Child
  • Child, Preschool
  • Complement Pathway, Alternative (immunology)
  • Erythrocytes (immunology, metabolism, parasitology)
  • Female
  • Flow Cytometry
  • Hemolysis (immunology)
  • Humans
  • India
  • Lectins (immunology)
  • Leishmania (immunology)
  • Leishmaniasis, Visceral (blood, immunology)
  • Male
  • Middle Aged
  • Polysaccharides (immunology)
  • Sialic Acids (biosynthesis, blood, immunology)

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