Permeability characteristics of complement-damaged membranes: evaluation of the membrane leak generated by the complement proteins C5b-9

Abstract

Permeability characteristics of the membrane lesion generated by the terminal complement proteins are considered in light of recent observations that the measured diffusion of solute across complement-damaged membranes does not conform to the "doughnut hole" model of a discrete transmembrane pore formed by the inserted C5b-9 complex. By using the measured kinetics of steady-state tracer isotope diffusion of nonelectrolytes across resealed erythrocyte ghost membranes treated with C5b-9, a new transport model is developed. This model considers the apparent membrane lesion strictly in terms of the operational criteria of a functional conducting pathway for the observed diffusing solute, independent of a priori assumptions about the geometry or molecular properties of the membrane lesion. With this definition of the unit membrane lesion and the assumption that the exclusion size of the conducting pathway varies directly with the multiplicity of bound C5b-9 (as suggested by previous measurements under conditions of varying input of C5b-9), numerical estimates of te apparent permeability of the complement-damaged membrane to four diffusing nonelectrolytes are derived. These results suggest that the pathway for a particle diffusing across the complement lesion cannot be a pore and is functionally equivalent to an aqueous leak pathway, free of pore constraints. Implications of these results are discussed in terms of current molecular models for the mechanism of membrane damage by the complement proteins.