Recognition of the major cell surface glycoconjugates of Leishmania parasites by the human serum mannan-binding protein.
Activation of complement on the surface of parasitic protozoa of the genus Leishmania appears to be important for parasite infectivity in the mammalian host, as it allows these parasites to attach to and invade macrophages via their surface complement receptors. Serum mannan-binding protein (MBP) is a known activator of complement. Therefore, in the present study, we have investigated whether serum MBP binds to live Leishmania parasites, and to mannose-containing saccharides derived from the parasite cell surface. We have observed by fluorescence microscopy that biotinylated MBP binds to the surface of L. major and L. mexicana promastigotes. At this developmental stage the parasites are coated by a mannose-containing lipophosphoglycan (LPG). We have observed that radioiodinated MBP binds in a mannose-inhibitable manner to purified LPG which has been immobilized in plastic microwells, as well as to purified mannose-terminating di-, tri- and tetrasaccharide fragments ('cap' structures) which have been released by mild acid hydrolysis from the outer chains of the LPG, converted into neoglycolipids and resolved by thin-layer chromatography. 125I-MBP also binds in the chromatogram-binding assay to the mannose-containing glycoinositol-phospholipids that are expressed in high copy number on both the promastigote and the intracellular amastigote stages of most Leishmania species. These data suggest that MBP has the potential to opsonize the major developmental stages of Leishmania parasites, and provide a possible mechanism for the antibody-independent activation of complement on their surface.
Green
P J
PJ
Glycoconjugates Section, MRC Clinical Research Centre, Harrow, Middlesex, UK.
Feizi
T
T
Stoll
M S
MS
Thiel
S
S
Prescott
A
A
McConville
M J
MJ
D000818:Animals; D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000097:blood* / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D037222:Collectins; D003167:Complement Activation; D006001:Glycoconjugates / Q000737:chemistry / Q000276:immunology*; D006028:Glycosphingolipids / Q000737:chemistry / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007891:Leishmania / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D018320:Leishmania major / Q000276:immunology; D007894:Leishmania mexicana / Q000276:immunology; D007896:Leishmaniasis / Q000209:etiology; D008351:Mannans / Q000378:metabolism*; D008969:Molecular Sequence Data; D009895:Opsonin Proteins / Q000097:blood; D010587:Phagocytosis
D002352:Carrier Proteins; D037222:Collectins; D006001:Glycoconjugates; D006028:Glycosphingolipids; D008351:Mannans; D009895:Opsonin Proteins; C008290:lipophosphonoglycan