H. Abdelghaffar et al., COMPARISON OF VARIOUS MACROLIDES ON STIMULATION OF HUMAN NEUTROPHIL DEGRANULATION IN-VITRO, Journal of antimicrobial chemotherapy, 38(1), 1996, pp. 81-93
Macrolide antibiotics are taken up and concentrated by host cells, par
ticularly phagocytes, and are likely candidates to modify cell functio
ns. In this study, we extended our previous work concerning the effect
of three 14-membered-ring macrolides (dirithromycin, erythromycin and
erythromycylamine) on human neutrophil exocytosis, and found that thr
ee other erythromycin A derivatives (roxithromycin, clarithromycin and
the azalide, azithromycin) also triggered neutrophil degranulation in
a time- and concentration-dependent manner. After 30 min of incubatio
n, the correlation coefficients for concentration-dependence for roxit
hromycin were 0.885, 0.739 and 0.750 (P < 0.005) and for clarithromyci
n were 0.795, 0.599, 0.733 (P < 0.02), respectively, for lysozyme, bet
a-glucuronidase and lactoferrin release. Although the underlying mecha
nism was not elucidated, these and previous data suggest that intracel
lular accumulation is a prerequisite. Furthermore, comparison of the c
haracteristics of macrolide-induced exocytosis with those of exocytosi
s triggered by the synthetic chemotactic stimulus FMLP suggested that
different mechanisms are involved. In keeping with this possibility, w
e showed that combined treatment (macrolides plus FMLP) resulted in to
tally additive exocytosis of azurophilic but not specific granules. Th
e clinical relevance of our data remains to be ascertained.