Transient changes in erythrocyte membrane permeability are induced by sublytic amounts of the complement membrane attack complex (C5b-9).
We have previously shown that sublytic heterologous complement induces large but transient increases in erythrocyte membrane permeability. We now report that when erythrocytes are bystanders in zymosan-activated autologous serum, they increase their Na+ permeability 10-fold, indicating that autologous complement can also induce transient membrane lesions. When we isolated the effect of the C5b-9 membrane attack complex of complement by using human C5b-9 assembled from purified components, we found there was minimal lysis but efficient Na+ uptake. Suspension of the sublytically damaged erythrocytes in K+ medium caused the cells to lyse, which is consistent with the cells recruiting a compensatory K+ efflux similar to that observed when human erythrocytes were exposed to heterologous complement. Sublytic C5b-9 exposure also became lytic when extracellular Ca2+ was limited and when the cells were exposed to charybdotoxin, an inhibitor of the Ca(2+)-activated K+ channel. This indicates that Ca2+ is required for the functional termination of the C5b-9 lesion. We also show that the membrane hyperpolarization resulting from activation of the Ca(2+)-dependent K+ efflux does not influence the termination of the C5b-9 lesion. Thus, the influx of Ca2+ through the complement lesion initiates at least two apparently independent adaptive responses: (1) a process that terminates the leak; and (2) a K+ efflux that has a volume regulatory function. Our data support the potential of the sublytic C5b-9 lesion to act as a physiologic mediator for autologous erythrocytes.
Halperin
J A
JA
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Taratuska
A
A
Rynkiewicz
M
M
Nicholson-Weller
A
A
D002118:Calcium / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000502:physiology*; D018999:Charybdotoxin; D003186:Complement C9 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000008:administration & dosage / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials; D011188:Potassium / Q000097:blood; D015221:Potassium Channels / Q000502:physiology; D012604:Scorpion Venoms / Q000494:pharmacology; D012964:Sodium / Q000097:blood; D015054:Zymosan / Q000494:pharmacology
D003186:Complement C9; D015938:Complement Membrane Attack Complex; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D015054:Zymosan; D012964:Sodium; D011188:Potassium; D002118:Calcium