Lysis of sensitized sheep erythrocytes in human sera deficient in the second component of complement.
Analysis of C-dependent lysis of sensitized SRBC by C2-deficient sera (C2D) led to the characterization of a C2 bypass pathway. Lysis in the total hemolytic C assay by C2D sera was Ca2+-dependent and required a high concentration of hemolysin to sensitize E. Selective component depletion indicated a requirement for C1 and C4 of the classical pathway (CP) and proteins B, P, and probably D of the alternative pathway (AP). Total hemolytic C could be restored to normal in these C2D sera by utilizing heavily sensitized E or by the addition of a supranormal concentration of B. This system most closely resembles a pathway described by J. E. May and M. M. Frank which requires antibody, C1, and the AP but not C4 or C2. It differs in its requirement for C4. We hypothesize that this pathway represents vestiges of a more primitive C pathway. It becomes evident and possibly clinically important in the setting of C2 deficiency, by allowing C activation, other than the AP, and perhaps in normal individuals, by damaging microorganisms that have evolved means to inhibit early components of the CP.
Knutzen Steuer
K L
KL
Howard Hughes Medical Institute Laboratories, Washington University School of Medicine, St. Louis, MO 63110.
Sloan
L B
LB
Oglesby
T J
TJ
Farries
T C
TC
Nickells
M W
MW
Densen
P
P
Harley
J B
JB
Atkinson
J P
JP
D000328:Adult; D000818:Animals; D003166:Complement Activating Enzymes / Q000378:metabolism; D003167:Complement Activation; D003172:Complement C1 / Q000378:metabolism; D015922:Complement C1q; D003175:Complement C2 / Q000172:deficiency*; D003181:Complement C4 / Q000378:metabolism; D003170:Complement Pathway, Alternative; D004492:Edetic Acid; D004533:Egtazic Acid; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006461:Hemolysis; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012756:Sheep
D003172:Complement C1; D003175:Complement C2; D003181:Complement C4; D004533:Egtazic Acid; D015922:Complement C1q; D004492:Edetic Acid; D003166:Complement Activating Enzymes