COMPLEMENT ACTIVATION IN-VITRO BY THE RED-CELL SUBSTITUTE, LIPOSOME-ENCAPSULATED HEMOGLOBIN - MECHANISM OF ACTIVATION AND INHIBITION BY SOLUBLE COMPLEMENT RECEPTOR-TYPE-1

BACKGROUND: Liposome-encapsulated hemoglobin (LEH) has been developed as an emergency blood substitute, yet its effect on human complement h as never been explored. Considering that complement activation is a ma jor pathogenic factor in the respiratory distress syndrome that often develops in trauma and shock, LEH-induced complement activation may be a critical safety issue. STUDY DESIGN AND METHODS: Various LEH and co rresponding empty liposomes were incubated with normal human sera, and various markers of complement activation (serum levels of C4d, Bb, SC 5b-9, and CH50; C5a-induced granulocyte aggregation; membrane depositi on of C3b) were measured. Incubations were also performed in the prese nce of (ethylene-bis[oxyethylenenitrilo]tetraacetic acid) (EGTA) and M g++ (EGTA/Mg++) and soluble complement receptor type 1. RESULTS: LEH a nd liposomes activated human complement, as indicated by significant c hanges in one or more markers. The effect was primarily due to the pre sence of the phospholipid vehicle; small, unilamellar, highly homodisp ersed vesicles induced the greatest degree of complement activation. C omplement activation was partially inhibited by EGTA/Mg++. The latter finding, together with the parallel increases in serum C4d and Bb, sug gests activation of both the classical and alternative pathways. Solub le complement receptor type 1 (0.05-20 mu g/mL) efficiently inhibited all vesicle-induced complement activation. CONCLUSION: Because of comp lement activation, the use of LEH for transfusion may require careful evaluation of safety. Soluble complement receptor type 1 may be useful as a prophylactic agent for complement activation-related complicatio ns of liposome infusions.