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

A.  BEE  a1, F. J.  CULLEY  a2, I. S.  ALKHALIFE  a1, K. B.  BODMAN-SMITH  a2, J. G.  RAYNES  a2 and P. A.  BATES  a1 c1
a1 Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
a2 Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK

Article author query
bee a   [PubMed][Google Scholar] 
culley f   [PubMed][Google Scholar] 
alkhalife i   [PubMed][Google Scholar] 
bodman-smith k   [PubMed][Google Scholar] 
raynes j   [PubMed][Google Scholar] 
bates p   [PubMed][Google Scholar] 


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.

(Received July 11 2000)
(Revised October 23 2000)
(Accepted November 6 2000)

Key Words: Leishmania mexicana; metacyclic promastigote; C-reactive protein; lipophosphoglycan; amastigote; adenylate cyclase.

c1 Corresponding author: Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK. Tel: +44 151 708 9393. Fax: +44 151 708 9007. E-mail: