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Transformation of Leishmania mexicana metacyclic promastigotes to amastigote-like forms mediated by binding of human C-reactive protein

Published online by Cambridge University Press:  07 August 2001

A. BEE ,
F. J. CULLEY ,
I. S. ALKHALIFE ,
K. B. BODMAN-SMITH ,
J. G. RAYNES  and
P. A. BATES
A. BEE
Affiliation:
Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
F. J. CULLEY
Affiliation:
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
I. S. ALKHALIFE
Affiliation:
Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
K. B. BODMAN-SMITH
Affiliation:
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
J. G. RAYNES
Affiliation:
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
P. A. BATES
Affiliation:
Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
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Abstract

Infective metacyclic promastigote forms of Leishmania mexicana are introduced by the bite of sandfly vectors into their human hosts where they transform into the amastigote form. The kinetics of this process was examined in vitro in response to different combinations of temperature (26 °C or 32 °C), pH (7.2 or 5.5), and exposure to human serum. Little transformation occurred at 26 °C/pH 7.2, intermediate levels at 26 °C/pH 5.5 and 32 °C/ pH 7.2, and the greatest response at 32 °C/pH 5.5. Transformation was stimulated by exposure to normal human serum, but was markedly reduced when serum previously incubated at 56 °C for 1 h was used (complement heat-inactivated). This stimulatory effect was reproduced by exposure to a single purified component of human serum, C-reactive protein (CRP). Binding of CRP to the whole surface of L. mexicana metacyclic promastigotes, including the flagella, was demonstrated by an indirect fluorescent antibody test. The effect of purified CRP was dose dependent and occurred using normal serum concentrations. The stimulatory effect of whole serum was oblated by CRP depletion and restored by addition of purified CRP. The effects of cAMP analogues indicated that transformation could be mediated via an adenylate cyclase cascade.

Keywords

Leishmania mexicanametacyclic promastigoteC-reactive proteinlipophosphoglycanamastigoteadenylate cyclase
Type
Research Article
Information
Parasitology , Volume 122 , Issue 5 , May 2001 , pp. 521 - 529
Copyright
2001 Cambridge University Press

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