@article{fdi:010037938, title = {{D}istinct roles of haptoglobin-related protein and apolipoprotein {L}-1 in trypanolysis by human serum}, author = {{V}anhollebeke, {B}. and {N}ielsen, {M}. {J}. and {W}atanabe, {Y}. and {T}ruc, {P}hilippe and {V}anhamme, {L}. and {N}akajima, {K}. and {M}oestrup, {S}. {K}. and {P}ays, {E}.}, editor = {}, language = {{ENG}}, abstract = {{A}polipoprotein {L}-{I} (apo{L}-{I}) is a human high-density lipoprotein ({HDL}) component able to kill {T}rypanosoma brucei brucei by forming anion-selective pores in the lysosomal membrane of the parasite. {A}nother {HDL} component, haptoglobin-related protein ({H}pr), has been suggested as an additional toxin required for full trypanolytic activity of normal human serum. {W}e recently reported the case of a human lacking apo{L}-{I} (apo{L}-{I}-/-{HS}) as the result of frameshift mutations in both apo{L}-{I} alleles. {H}ere, we show that this serum, devoid of any trypanolytic activity, exhibits normal concentrations of {HDL}-bound {H}pr. {C}onversely, the serum of individuals with normal {HDL}-bound apo{L}-{I} but who lack {H}pr and haptoglobin [{H}p(r)-/-{HS}] as the result of gene deletion (anhaptoglobinemia) exhibited phenotypically normal but delayed trypanolytic activity. {T}he trypanolytic properties of {H}p(r)-/-{HS} were mimicked by free recombinant apo{L}-{I}, whereas recombinant {H}pr did not affect trypanosomes. {T}he lysis delay observed with either {H}p(r)-/-{HS} or recombinant apo{L}-{I} could entirely be attributed to a defect in the uptake of the lytic components. {T}hus, apo{L}-{I} is responsible for the trypanolytic activity of normal human serum, whereas {H}pr allows fast uptake of the carrier {HDL} particles, presumably through their binding to an {H}p/{H}pr surface receptor of the parasite.}, keywords = {innate immunity ; sleeping sickness ; trypanolytic factor ; haptoglobin receptor ; {T}rypanosoma brucei}, booktitle = {}, journal = {{P}roceedings of the {N}ational {A}cademy of {S}ciences of the {U}nited {S}tates of {A}merica}, volume = {104}, numero = {10}, pages = {4118--4123}, ISSN = {0027-8424}, year = {2007}, DOI = {10.1073/pnas.0609902104}, URL = {https://www.documentation.ird.fr/hor/fdi:010037938}, }