Conformationally altered hyaluronan restricts complement classical pathway activation by binding to C1q, C1r, C1s, C2, C5 and C9, and suppresses WOX1 expression in prostate DU145 cells.
Linear non-sulfated hyaluronan (HA) does not bind complement proteins yet inhibits their hemolytic function. We have previously induced the complement inhibitory function of HA by heat treatment. However, heated HA readily loses its anti-complementary activity probably due to instantaneous interchain re-association. Here, HA solutions were heated and then freeze-dried. Compared to native HA, heated/freeze-dried HA stably restricted serum complement-mediated hemolysis via the classical pathway, in which serum C1 hemolytic function and C3 activation were blocked. Also, treated HA had a significantly increased binding of component C1q, C1r, C1s, C2, C5, C9, P, D and H. Further, when HA was gel-fractionated by electrophoresis and then freeze-dried, its anti-complementary activity was stably induced. Both native and heated/freeze-dried HA stimulated ERK phosphorylation in prostate DU145 cells. However, treated HA suppressed the expression of tumor suppressors WOX1 and WOX2. Together, HA with an altered conformation stabilizes its inhibition and binding of complement proteins. It may recognize cell surface receptors differently from native HA, thereby differentially regulating the expression of cellular proteins.
Hong
Qunying
Q
Guthrie Research Institute, Laboratory of Molecular Immunology, 1 Guthrie Square, Sayre, PA 18840, USA.
Kuo
Emory
E
Schultz
Lori
L
Boackle
Robert J
RJ
Chang
Nan-Shan
NS
D045744:Cell Line, Tumor; D003167:Complement Activation / Q000187:drug effects; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000378:metabolism*; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005612:Freeze Drying; D005782:Gels / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D008968:Molecular Conformation; D010088:Oxidoreductases / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase
D005782:Gels; D025521:Tumor Suppressor Proteins; D006820:Hyaluronic Acid; D003165:Complement System Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; D048049:Extracellular Signal-Regulated MAP Kinases