O. Levy et al., INDIVIDUAL AND SYNERGISTIC EFFECTS OF RABBIT GRANULOCYTE PROTEINS ON ESCHERICHIA-COLI, The Journal of clinical investigation, 94(2), 1994, pp. 672-682
Affinity purification of crude acid extracts of rabbit polymorphonucle
ar leukocytes using Escherichia coli (J5) as adsorbent yields the bact
ericidal/permeability-increasing protein (BPI), two 15-kD species (p15
s), and the two most potent (cationic) defensin species (neutrophil pe
ptides [NP]-1 and -2). Tested in buffered isotonic medium, the relativ
e antibacterial potency of these proteins against E. coli J5 is BPI (I
C50 0.2 nM) > p15A (10 nM) > NP-1 (400 nM). Sublethal doses of p15A or
NP-1 can synergize with BPI to decrease the dose required to inhibit
the growth of E. coli by up to 50-fold. BPI and p15A display similar f
eatures of antibacterial action distinct from defensin NP-1, but NP-1
acts synergistically only with BPI and not with p15A. All aspects of t
he combined action of BPI and NP-1 resemble those observed with higher
concentrations of BPI alone, implying that NP-1 enhances BPI potency.
Neither NP-1 nor p15A alter the amount of BPI binding to E. coil but
BPI enhances binding of p15A to E. coli, raising the possibility that
synergy between these two proteins may occur at least partially at the
level of binding. The potent synergistic actions of these proteins ca
n also be demonstrated against serum-resistant clinical isolates of en
capsulated E. coli tested in whole blood and plasma ex vivo, suggestin
g that such combined action may contribute to host defense in vivo.