Hemolysis rates of human erythrocytes induced by C2 and C8-C14 straight chain 1-alkanols, 1,2-alkanediols and the corresponding
benzylidene derivatives (
benzaldehyde acetals) have been studied and compared with
hemolysis rates obtained by three
peptide toxins. The peak of activity occurs at C12 for the alkanols and
glycols and at C10 for the
benzylidene derivatives. The most active compound is
1-dodecanol, followed by 1,2-dodecanediol and the C10 benzylidene
acetal, which show 50%
hemolysis at 15, 99 and 151 microM, respectively, at 37 degrees C. A few
lysolecithins and longer chain cis-unsaturated
alcohols were studied for comparison purposes, and were found to be more active than
1-dodecanol. The most active were the 16:0
lysolecithin and cis-9-tetradecene-1-ol, which gave 50%
hemolysis at concentrations of 2.8 and 5.6 microM respectively. The hemolytic activities of
1-dodecanol, 1,2-dodecanediol and the C10 benzylidene
acetal were compared to activities of Pyrularia
thionin and
melittin with cow, horse, sheep, pig and human erythrocytes. Whereas the
peptide toxins showed clear specificity for human erythrocytes, no selectivity was shown by any of the other compounds tested. Addition of the
thionin or Naja naja kaouthia
cardiotoxin to erythrocyte ghosts caused a slight but reproducible increase in the order of the
phospholipid bilayer, as measured with the
fluorescent probe NBD-PC.
Cardiotoxin gave a greater response than did the P
thionin, and extensively iodinated P
thionin gave a smaller change than did P
thionin. Similar results were obtained with
melittin, but this
peptide gave a markedly greater response than all other
peptides. Addition of
dodecanol or the C10 benzylidene
acetal caused a marked increase in membrane fluidity. All of these data indicate that the organic compounds interact directly with and are incorporated nonspecifically into the
membrane lipid bilayer, but the
peptide toxins interact specifically with some component on the surface of the membrane, either a
protein or specific
phospholipid domain, followed by insertion into the membrane and decreasing
phospholipid movement.