Inhibition of the function of activated properdin by squid chondroitin sulfate E glycosaminoglycan and murine bone marrow-derived mast cell chondroitin sulfate E proteoglycan.
We compared the relative capacities of two over-sulfated glycosaminoglycans, heparin and chondroitin sulfate E, to alter the function of native properdin (nP) and activated properdin (aP) in the formation and stabilization of the amplification C3 convertase (C3b,Bb). Heparin was more active on a weight basis than chondroitin sulfate E in inhibiting the formation of C3b,Bb without or with nP, but had no influence on the decay of a pre-formed convertase, either unstabilized or stabilized with nP or aP. In contrast, chondroitin sulfate E was over 10-fold more active than heparin in preventing the formation of C3b,Bb in the presence of aP, and gave dose-related acceleration of decay of pre-formed C3b,Bb,aP but not of unstabilized or nP-stabilized pre-formed convertase. The inhibitory effect of both glycosaminoglycans on the formation of C3b,Bb in the presence of nP or aP was less when the number of C3b sites per target cell was increased. The preferential action of chondroitin sulfate E on the function of aP during the formation and decay of C3b,Bb,aP as compared to C3b,Bb,nP implies functional differences in the two forms of P even when they have been incorporated into C3b,Bb. The equal potency, when adjusted for uronic acid content, of chondroitin sulfate E proteoglycan isolated from the T cell-dependent, bone marrow-derived murine mast cell and of chondroitin sulfate E glycosaminoglycan from squid reveals that the linkage of the glycosaminoglycan to a peptide core does not diminish its regulatory action on the alternative complement pathway.
D000818:Animals; D001667:Binding, Competitive; D001854:Bone Marrow Cells; D002809:Chondroitin Sulfates / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects*; D003179:Complement C3b / Q000096:biosynthesis / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000494:pharmacology; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D049832:Decapodiformes; D004305:Dose-Response Relationship, Drug; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D011414:Properdin / Q000037:antagonists & inhibitors* / Q000502:physiology; D013552:Swine
D003180:Complement C3b Inactivator Proteins; D006025:Glycosaminoglycans; C038142:chondroitin sulfate glycosaminoglycan; D011414:Properdin; D003179:Complement C3b; D006493:Heparin; D002809:Chondroitin Sulfates