Degradation of the P0, P1, and Pr proteins in peripheral nervous system myelin by plasmin: implications regarding the role of macrophages in demyelinating diseases.
Activated macrophages secrete a variety of neutral proteinases, including plasminogen activator. Since macrophages are implicated in primary demyelination in the peripheral nervous system (PNS) in Guillain-Barré syndrome and experimental allergic neuritis, we have investigated the ability of plasmin and of conditioned media from cultured macrophages, in the presence of plasminogen, to degrade the proteins in bovine and rat PNS myelin. The results indicate that (a) the major glycoprotein P0 and the basic P1 and Pr proteins in PNS myelin are extremely sensitive to plasmin, perhaps more so than is the basic protein in CNS myelin; (b) the initial product of degradation of P0 by plasmin has a molecular weight higher than that of the "X" protein; (c) large degradation products of P0 are relatively insensitive to further degradation; and (d) the neuritogenic P2 protein in PNS myelin is quite resistant to the action of plasmin. Results similar to those with plasmin were obtained with conditioned media from macrophages and macrophage-like cell lines together with plasminogen activator, and the degradation of the PNS myelin proteins, Po and P1, under these conditions was inhibited by p-nitrophenylguanidinobenzoate, an inhibitor of plasmin and plasminogen activator. The results suggest that the macrophage plasminogen activator could participate in inflammatory demyelination in the PNS.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D003711:Demyelinating Diseases / Q000097:blood*; D005341:Fibrinolysin / Q000378:metabolism*; D066298:In Vitro Techniques; D008264:Macrophages / Q000201:enzymology*; D008970:Molecular Weight; D004676:Myelin Basic Protein / Q000378:metabolism*; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000378:metabolism*; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D013126:Spinal Nerve Roots / Q000378:metabolism
D004676:Myelin Basic Protein; D018993:Myelin P0 Protein; D009185:Myelin Proteins; C031633:myelin basic protein P1; C031634:myelin basic protein Pr; D005341:Fibrinolysin