Potentiation of liposome-induced complement activation by surface-bound albumin.
Large anionic multilamellar liposomes containing 71% membrane cholesterol (MLV) caused complement (C) activation in human serum in vitro, as reflected in significant rises in S protein-bound terminal complex (SC5b-9) and C3a-desarg levels. Increasing the albumin content in serum by 1-4 g/100 ml led to 50-100% further increase in MLV-induced C activation, while higher amounts of exogenous human serum albumin (HSA) gradually lost the capability to potentiate liposomal C activation. HSA alone had no influence on SC5b-9 formation at any level below 12%. Complement activation by liposomes and the potentiating effect of supplemental HSA were greatly reduced or eliminated in the absence of C1q or in the presence of 10 mM EGTA/2.5 mM Mg(2+), pointing to the involvement of the classical pathway. Potentiation of C activation by supplemental HSA was not unique to MLV-induced activation, as deposition of HSA on the membrane of "Centricon" ultrafiltration units also potentiated the C-activating effect of the polycarbonate membrane. Fatty acid (FA) or non-monomeric protein contamination in HSA were unlikely to be playing a role in the described effects, as 96% pure, FA-rich (Buminate) and 99% pure, FA-free HSA had identical effects on liposomal C activation. While highlighting a new modulatory mechanism on liposomal C activation, the above data raise the possibility that deposition of extravasated HSA at sites of tissue injury may serve a hitherto unrecognized proinflammatory function.
Savay
Sandor
S
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7580, USA.
Szebeni
Janos
J
Baranyi
Lajos
L
Alving
Carl R
CR
D002254:Carbonates / Q000737:chemistry; D003167:Complement Activation / Q000187:drug effects; D015922:Complement C1q / Q000737:chemistry / Q000172:deficiency; D004357:Drug Synergism; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D006801:Humans; D008081:Liposomes; D012709:Serum Albumin / Q000737:chemistry* / Q000494:pharmacology; D013499:Surface Properties
D002254:Carbonates; D005230:Fatty Acids, Nonesterified; D008081:Liposomes; D012709:Serum Albumin; D015922:Complement C1q