title: C1q binding to liposomes is surface charge dependent and is inhibited by peptides consisting of residues 14-26 of the human C1qA chain in a sequence independent manner.
abstract: Complement activation by anionic liposomes proceeds by antibody-independent, C1q-initiated activation of the classical pathway. Purified C1q bound to anionic liposomes in an acidic lipid concentration-dependent manner. Saturation binding, but not the apparent association constant, was enhanced by increasing the cardiolipin content of the liposomes or decreasing either the pH or ionic strength of the reaction mixture. These observations indicate the involvement of electrostatic factors in the binding. A highly cationic region in the collagen-like domain of C1q comprised of residues 14-26 of the C1qA polypeptide chain was assessed for involvement in liposome binding. This region has previously been shown to mediate C1q binding to other immunoglobulin-independent activators of the classical pathway of complement. Peptides containing residues 14-26 of C1qA, denoted C1qA14-26, inhibited C1q binding to and complement activation by anionic liposomes. The inhibitory capacity of these cationic peptides had no sequence or conformation specificity. Rather, the amount of positive charge on the peptides was the determining factor. When present in excess, peptides with five cationic residues inhibited C1q binding and complement activation; however, C1q peptides with only two cationic residues did not. In addition to the C1qA14-26 region, other parts of C1q that contain cationic residues may also be involved in C1q binding to anionic liposomes.
authors: Department of Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
authors: A J
authors: AJ
authors: Bradley
authors: D E
authors: DE
authors: Brooks
authors: R
authors: R
authors: Norris-Jones
authors: D V
authors: DV
authors: Devine
mesh_terms: D003167:Complement Activation / Q000187:drug effects; D015922:Complement C1q / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D009994:Osmolar Concentration; D010455:Peptides / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D008081:Liposomes; D010455:Peptides; D010743:Phospholipids; D015922:Complement C1q