ABSTRACT

I. Introduction.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .208

111. Pore Size Heterogeneity of the Complement Lesion . . . . . . . . . . . . . . . . . . . . . . . . . . . ,210

IV. Relationship of Pore Size to the Lytic Effect of C8, C9, and Poly C9 in the Membrane Attack Complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 10

VIII. Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 17

I. INTRODUCTION

The membrane attack complex (MAC) of complement is composed of the terminal complement proteins C5b through C9. Two different general mechanisms may participate in the production of the cytolytic effect of the MAC on target membranes. One involves removal of lipids from the target membrane and is a consequence of the high affinity of the MAC for membrane lipids. The other mechanism is due to channel formation in the target membrane. It appears that the MAC can generate two different types of transmembrane channels. One is a "lipid channel" which is caused by the binding of membrane lipids to the components of the MAC, resulting in disorganization of the lipid bilayer, with channel formation at the interphase between the MAC-bound lipids and the lipid bilayer. The other type consists of tubular structures composed of polymers of C9 (poly C9) which penetrate the membrane and function as "protein channels". In addition to forming protein channels, because of the high affinity for membrane lipids, the poly C9 structure may also create lipid channels.