Internalization and degradation of receptor bound C-reactive protein by U-937 cells: induction of H2O2 production and tumoricidal activity.
The presence of a membrane receptor for C-reactive protein (CRP-R) on the human monocytic cell line U-937 was the basis for determining the metabolic fate of the receptor-bound ligand and the functional response of the cells to CRP. Internalized [125I]CRP was measured by removing cell surface-bound [125I]CRP with pronase. Warming cells to 37 degrees C resulted in the internalization of approx. 50% of the receptor-bound [125I]CRP or receptor-bound [125I]CRP-PC-KLH complexes. U-937 cells degraded about 25% of the internalized [125I]CRP into TCA-soluble radiolabeled products. The lysosomotrophic agents (chloroquine, NH4Cl) greatly decreased the extent of CRP degradation without altering binding or internalization. In addition, a pH less than 4.0 resulted in dissociation of receptor-bound [125I]CRP. Treatment of U-937 cell with monensin, a carboxylic ionophore which prevents receptor recycling, resulted in accumulation of internalized [125I]CRP. Therefore, it appears that the CRP-R complex is internalized into an endosomal compartment where the CRP is uncoupled from its receptor and subsequently degraded. CRP initiated the differentiation of the U-937 cells so that they acquired the ability to produce H2O2 and also display in vitro tumoricidal activity. The results support the concept that internalization and degradation of CRP leads to the activation of monocytes during inflammation.
Tebo
J M
JM
Department of Microbiology, Ohio State University, Columbus 43210.
Mortensen
R F
RF
D000643:Ammonium Chloride / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism*; D002451:Cell Compartmentation / Q000187:drug effects; D016923:Cell Death; D002454:Cell Differentiation; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D004705:Endocytosis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008985:Monensin / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000473:pathology; D011971:Receptors, Immunologic / Q000378:metabolism*
C071581:CRP protein, human; D011971:Receptors, Immunologic; D000643:Ammonium Chloride; D002738:Chloroquine; D002097:C-Reactive Protein; D008985:Monensin; D006861:Hydrogen Peroxide