Characterisation of the receptor for the macrophage colony-stimulating factor in monocytes/macrophages of patients congenitally infected with Trypanosoma cruzi.
Trypanosoma cruzi, the aetiological agent of Chagas' disease, is able to parasitise almost any type of cell in the mammalian host. Only the macrophage, however, is potentially microbicidal for the parasite. The effectiveness of macrophages in killing T. cruzi appears to be related to the degree of activation of the cell. The macrophage colony-stimulating factor (MCSF) is a glycoprotein that promotes proliferation, differentiation and activation of macrophages. It acts through a cell-surface receptor that encodes a tyrosine kinase in its cytoplasmic domain. The MCSF receptor (MCSFR) autophosphorylates upon induction with the ligand. A three to seven-fold lower degree of phosphorylation of ligand-stimulated MCSFR in monocytes/macrophages of patients with chronic Chagas' disease compared with those of healthy donors has been previously demonstrated. Only 5-10% of the population infected with T. cruzi develop chronic Chagas' disease. Furthermore, members of this group have a functional defect of the MCSFR. I therefore decided to investigate the state of the MCSFR in patients congenitally infected with T. cruzi in whom the acute phase of the disease had subsided and who had subsequently become seronegative for Chagas' disease after treatment with Nifurtimox. I found a heterogeneous pattern of ligand-stimulated phosphorylation of MCSFR ranging from a nil to a six-fold difference within the population. Healthy children born to mothers with Chagas' disease showed a fully phosphorylated receptor protein after stimulation with MCSFR. The state of the MCSFR may correlate with the potential to develop Chagas' disease.
Orchansky
P L
PL
Institute of Biochemistry INIBIBB, Bahia Blanca, Argentina.
D000293:Adolescent; D000328:Adult; D000818:Animals; D001118:Argentina; D014355:Chagas Disease / Q000151:congenital / Q000378:metabolism* / Q000469:parasitology; D002648:Child; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011233:Precipitin Tests; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000302:isolation & purification
D008024:Ligands; D016186:Receptor, Macrophage Colony-Stimulating Factor