Phagocytosis of P. falciparum malarial pigment hemozoin by human monocytes inactivates monocyte protein kinase C.
Hemozoin (malarial pigment) is a ferriprotoporphyrin IX-rich hemoglobin degradation product present in parasitized RBC. Avidly phagocytosed hemozoin abolishes phagocyte TPA-induced oxidative burst. Membrane-associated PKC increased transiently in hemozoin-fed monocytes by 50% after 30 min and decreased irreversibly to 20% of initial value within 5 h after phagocytosis. Control RBC-fed monocytes showed transient decay of membrane-associated PKC followed by complete recovery 12 h after phagocytosis. Cytosolic PKC was not impaired within 12 h and diminished drastically 24 h after phagocytosis of hemozoin. Results are compatible with increased degradation of membrane-translocated PKC, possibly by iron/H2O2-mediated damage of cysteine-rich regulatory domains of PKC.
Schwarzer
E
E
Dipartimento di Genetica, Biologia, Chimica Medica, Università di Torino, Italy.
Turrini
F
F
Giribaldi
G
G
Cappadoro
M
M
Arese
P
P
D000818:Animals; D002478:Cells, Cultured; D006420:Hemeproteins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D010587:Phagocytosis; D010860:Pigments, Biological / Q000378:metabolism* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000276:immunology* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D016897:Respiratory Burst
D006420:Hemeproteins; D010860:Pigments, Biological; C020753:hemozoin; D011493:Protein Kinase C