Blood, 15 April 2001, Vol. 97, No. 8, pp. 2530-2532
CORRESPONDENCE
To the editor:
Cationic peptides from leukocytes might kill bacteria by
activating their autolytic enzymes causing bacteriolysis: why are
publications proposing this concept never acknowledged?
A large series of publications1-9 has proposed that
cationic peptides from leukocytes kill bacteria primarily by causing a
depolarization of their membranes leading to enhanced permeability. One
group of cationic peptides from human neutrophils was even coined
bactericidal/permeability-increasing proteins.3
Surprisingly, however, none of a large series of other
publications that had proposed a concept that cationic agents from
neutrophils might be bactericidal also by virtue of their capacity to
activate the bacterial autolytic wall enzymes (muramidases), leading to
bacteriolysis and cell death,10-22 has ever been cited in
any of the publications by the leading authors in this field of
research.1-9
For the information of your readers, there exist a series of 16 publications since 1974 entitled "Effect of leukocyte hydrolases on
bacteria" and several additional publications on the same subject under different titles, many of them published in journals covered by
Medline; the references contain a selected list of
these.10-22,24 These had proposed that many of the
highly cationic agents either present in plasma or generated by
activated phagocytes (eg, lysozymes, PLA2, elastase, cathepsin G,
myeloperoxidase, bactericidal/permeability-increasing proteins,
defensins, etc) might kill bacteria not simply by acting on the
membranes to cause depolarization and enhanced
permeability1-7 but also by an indirect mechanism. This
involves a deregulation, by the cationic agents, of the anionic
and amphiphilic regulators of the autolytic wall enzymes
(muramidases) (lipoteichoic acid in Gram-positives and
Forssman antigens in Gram-negatives)16,17,23-25 resulting
in hydrolysis of the peptidoglycan, in bacteriolysis, and in cell
death. It is of great clinical importance that the bacteriolysis-inducing activity of cationic agents mimics that of
beta-lactam antibiotics.26 Furthermore, the observations that a variety of highly negatively charged, sulfated anionic agents
can act as potent inhibitors of the cationic agent- and beta-lactam-induced bacteriolysis11,12,14,16,17,27-30
further stress the importance of the autolytic systems in bacterial
killing. This phenomenon might also be of great clinical significance
especially in selecting measures to control postinfectious sequelae
that undoubtedly are triggered by the release of bacterial
components, especially following bacteriolysis.
Regrettably, attempts to bring these issues to the awareness of the
leading investigators in the field of cationic proteins1-9 and of clinicians involved is the clinical aspects of sepsis control have not been successful.
If the concept that cationic agents might be bactericidal also because
of their bacteriolysis-inducing properties is reasonable and
scientifically sound, it is expected that publications describing this
phenomenon should be cited by authors studying the bactericidal effects
of cationic agents. If on the other hand one deems that this concept is
for some reason erroneous, nonsensical, and scientifically unacceptable, such publications should definitely be cited
but properly discussed, challenged, and even also ridiculed. But it is
totally unacceptable and unreasonable that such publications be simply ignored!
Unfortunately, the avoidance of relevant citations and the disregard
for concepts that might perhaps not "fit" current dogma and beliefs
have reached epidemic levels. This is how pioneering publications
proposing "novel approaches and
ideas"16,17,29,30 to explain additional mechanisms of
microbial killing might be lost forever. More importantly, these
concepts will probably never reach the attention of clinicians
interested in the pathogenesis of inflammation, infection,
postinfectious sequelae, and the mechanisms of host
defense.29-31
But what is even more disturbing, concerning, and unacceptable is that
the expert referees selected by the editorial boards of journals and
who should have been knowledgeable of the relevant literature failed to
alert the authors to the existence of key publications on bacteriolysis
so relevant to the subject of the papers and of the reviews they had
been assigned to judge.
Am I wrong to assume that the task of a journal's editorial board is
to ensure that all viewpoints and ideas, both "conventional" and
nonconventional, be equally represented? Excuses either that limitations to the number of references permissible were the reason for
not citing basic and pioneering publications or that the authors had
been "instructed" to discuss only a narrow field of research and to
disregard others fields with direct relevance are unacceptable.
A failure to give credit to relevant papers is also unacademic,
self-defeating, unethical, and therefore unacceptable by all standards.
Furthermore, are papers older than 15 years, or so, already passé
and, therefore, unworthy of being acknowledged?
Isaac Ginsburg
Department of Oral Biology Hebrew University Jerusalem,
Israel
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