Biochemical alteration of membrane-associated IL-6 RI (80-kDa) in adherent macrophages and vascular endothelium

The potential biochemical mechanisms that mediate the ‘shedding’ of soluble IL-6 RI (80-kDa) receptor fragments in populations of adherent macrophages were explored. Stimulated macrophages displayed proportional increases in both the expression of membrane-associated IL-6 RI (80-kDa) and the release...

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Bibliographic Details
Published in:Molecular immunology 2001-09, Vol.38 (5), p.347-357
Main Authors: Coyne, C.P, Howell, Trey, Baravick, Jeff, Baravick, Erica, Willetto, Carla, Fenwick, Brad W
Format: Article
Language:English
Subjects:
Animals
Aspartic Acid Endopeptidases - antagonists & inhibitors
Buffers
Calcimycin - pharmacology
Cathepsin D - antagonists & inhibitors
Cattle
Cell Adhesion
Cell Membrane - metabolism
Citrates
Cysteine Proteinase Inhibitors - pharmacology
Cytokine receptors
Endothelium, Vascular - metabolism
Enzyme-proteases
Female
IL-6 RI (80-kDa)
interleukin 6 receptors
Leucine - analogs & derivatives
Leucine - pharmacology
Macrophages
Macrophages - cytology
Macrophages - drug effects
Macrophages - metabolism
N-Formylmethionine Leucyl-Phenylalanine - pharmacology
Pepstatins - pharmacology
Receptors, Interleukin-6 - metabolism
Shedding events
Sodium Citrate
Vascular endothelium
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Summary:The potential biochemical mechanisms that mediate the ‘shedding’ of soluble IL-6 RI (80-kDa) receptor fragments in populations of adherent macrophages were explored. Stimulated macrophages displayed proportional increases in both the expression of membrane-associated IL-6 RI (80-kDa) and the release of soluble receptor fragments. The use of protease inhibitors implicated thiol/cysteine and carboxyl/aspartate proteases in this process. Cathepsin-D depleted membrane-associated IL-6 RI (80-kDa) complexes and generated soluble receptor fragments. A carboxyl/aspartate protease from activated macrophages isolated utilizing pepstatin-A affinity chromatography, was also found to affect membrane-associated IL-6 RI (80-kDa) complexes and generate soluble receptor fragments. Most likely, this fraction corresponded to cathepsin-D based upon its origin, pepstatin-A binding avidity, Hb-PAGE zymography, and hydrolysis of an enzyme-specific substrate. We conclude that cathepsin-D can generate soluble fragments of IL-6 RI (80-kDa) expressed by both macrophages and vascular endothelium.
ISSN:0161-5890
1872-9142
DOI:10.1016/S0161-5890(01)00074-8