COMPARISON OF VARIOUS MACROLIDES ON STIMULATION OF HUMAN NEUTROPHIL DEGRANULATION IN-VITRO

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.