CEFDINIR (CL-983), A NEW ORAL AMINO-2-THIAZOLYL CEPHALOSPORIN, INHIBITS HUMAN NEUTROPHIL MYELOPEROXIDASE IN THE EXTRACELLULAR MEDIUM BUT NOT THE PHAGOLYSOSOME
Mt. Labro et al., CEFDINIR (CL-983), A NEW ORAL AMINO-2-THIAZOLYL CEPHALOSPORIN, INHIBITS HUMAN NEUTROPHIL MYELOPEROXIDASE IN THE EXTRACELLULAR MEDIUM BUT NOT THE PHAGOLYSOSOME, The Journal of immunology, 152(5), 1994, pp. 2447-2455
Cefdinir, a new oral 2-amino-5-thiazolyl cephalosporin, inhibited the
luminol-amplified chemiluminescence (LACL) response of human neutrophi
ls stimulated by PMA but not opsonized zymosan, in a concentration-dep
endent but not time-dependent manner. The LACL response to opsonized z
ymosan in cytochalasin B-treated neutrophils was, however, inhibited b
y cefdinir. Various cephalosporins, regardless of the presence of a 2-
amino-5-thiazolyl moiety, did not significantly alter the neutrophil L
ACL response triggered by PMA and zymosan. The LACL response induced b
y the calcium ionophore A23187 and FMLP was also impaired by cefdinir,
and this impairment was increased in cytochalasin B-treated neutrophi
ls. Superoxide anion generation by neutrophils, measured in terms of l
ucigenin-amplified chemiluminescence and cytochrome c reduction, was n
ot altered. Spontaneous and FMLP-induced neutrophil degranulation, ass
essed by lysozyme and p-glucuronidase release, were not modified by ce
finir. Furthermore, cefdinir inhibited LACL generation in cell-free sy
stems consisting of H2O2, Nal, and either horseradish peroxidase or a
myeloperoxidase-containing neutrophil extract. Orthodianisidine oxidat
ion in these two acellular systems was inhibited by cefdinir. Cefdinir
did not alter neutrophil bacterial killing at concentrations that inh
ibited myeloperoxidase-containing neutrophil extract-dependent reactio
ns induced by soluble stimuli. Taken together, these data strongly sug
gest that cefdinir directly inhibits the activity of myeloperoxidase-c
ontaining neutrophil extract released into the extracellular medium du
ring neutrophil stimulation by soluble mediators, but has no effect on
that released into the phagolysosome during phagocytosis. This unusua
l property of a member of the p-lactam family could be of interest in
modulating the exaggerated inflammatory process often associated with
infectious diseases.