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Effects of two macrolide antibiotics on human leukocyte membrane receptors and functions
1Medical Department B, Haukeland Hospital, University of Bergen, Norway.
Abstract:
Polymorphonuclear granulocytes (PMNs) and lymphocytes from healthy persons were incubated in varying concentrations of erythromycin and RU 28965, a new macrolide antibiotic. Incubation in erythromycin - even in high dilutions - caused a significant increase in the percentage of PMNs bearing receptors for the Fc portion of IgG (Fc gamma R) and for C3b (C3bR) as measured by rosette formation with EA (erythrocyte-antibody) and EAC (erythrocyte-antibody-complement) indicator cells. This effect could not be removed by extended washing of the cells. Incubation in RU 28965 had a similar effect, except for a decrease in EA and EAC rosetting cells at high concentrations (200 mg/l). Phagocytosis, as measured by chemiluminescence, and random migration of PMNs were unaffected by erythromycin. Chemotaxis under agarose was decreased after incubation in erythromycin or RU 28965. Erythromycin incubation increased the percentage of lymphocytes bearing receptors for sheep erythrocytes (E), but had no effect on the proportion of lymphocytes rosetting with EA or EAC, or on lymphocyte responses to mitogens PHA, conA, or PWM.
Insights
Erythromycin and a new macrolide antibiotic, RU 28965, enhanced immune cell receptors on polymorphonuclear granulocytes (PMNs) and lymphocytes. However, both antibiotics decreased PMN chemotaxis, impacting immune responses.
Area of Science:
- Immunopharmacology
- Cellular Immunology
Background:
- Erythromycin is a widely used macrolide antibiotic.
- The immunomodulatory effects of macrolides, including novel compounds like RU 28965, warrant investigation.
Purpose of the Study:
- To investigate the effects of erythromycin and RU 28965 on human polymorphonuclear granulocytes (PMNs) and lymphocytes.
- To assess the impact of these antibiotics on immune cell receptor expression, phagocytosis, migration, and chemotaxis.
Main Methods:
- Human PMNs and lymphocytes were incubated with varying concentrations of erythromycin and RU 28965.
- Immune cell receptor expression (Fc gamma R, C3bR, E receptors) was measured using rosette formation assays.
- Phagocytosis was assessed by chemiluminescence, and cell migration by random migration and chemotaxis under agarose.
- Lymphocyte responses to mitogens were evaluated.
Main Results:
- Erythromycin significantly increased Fc gamma R and C3bR expression on PMNs, while RU 28965 showed a similar effect with a decrease at high concentrations.
- Erythromycin incubation increased lymphocyte E receptor expression but did not affect EA or EAC rosetting or mitogen responses.
- Phagocytosis and random PMN migration were unaffected, but chemotaxis under agarose was decreased by both antibiotics.
Conclusions:
- Erythromycin and RU 28965 modulate immune cell function, primarily by altering receptor expression and impairing PMN chemotaxis.
- These findings suggest potential immunomodulatory roles for macrolide antibiotics beyond their antimicrobial activity.