Related Experiment Videos
Differential sensitivity of macrophages to bradykinin
S Böckmann1, K Mohrdieck, H Schmidt
1Institute of Pharmacology and Toxicology, University of Rostock, Germany.
Abstract:
In this report, we investigated the responsiveness of subpopulations of elicited peritoneal macrophages between each other compared to resident tissue macrophages of alveoli of guinea pig to the action of bradykinin. Bradykinin stimulated the secretion of superoxide radical, arachidonic acid and prostaglandin E2 (PGE2) via the bradykinin B2 receptor subtype in peritoneal macrophages, indicated by complete inhibitory effect of the bradykinin B2 receptor antagonist HOE 140. The extent of the secretion, however, varied substantially between macrophages of different size. The highest level of the secretion was observed in the fraction containing the intermediate-size macrophages, while progressively lower level of the secretion was observed with decreasing size. In contrast, large macrophages obviously lost their secretory ability. Additionally, the bradykinin-stimulated release of cyclooxygenase products exerted an inhibitory action on NADPH-oxidase activity depending on size and stage of maturation/activation of macrophages, as judged by an increase in superoxide radical generation by indomethacin (100 microM) preincubation of cells. Furthermore, the investigation of resident tissue macrophages of alveoli has shown that these cells also express the bradykinin B2 receptor subtype. However, the receptor activity measured by bradykinin-induced increase in intracellular free calcium [Ca2+]i was very low compared to elicited peritoneal macrophages. These findings indicate that the stage of differentiation/maturation and activation of macrophages may be important for the ability of bradykinin to stimulate these cells to inflammatory responses in vivo.
Insights
Bradykinin activates peritoneal macrophages to release inflammatory mediators via the B2 receptor. Macrophage size and maturation influence this response, with larger cells showing reduced activity compared to resident alveolar macrophages.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Macrophages play crucial roles in inflammatory responses.
- Bradykinin is a peptide involved in inflammation and pain signaling.
- Differential responses of macrophage subpopulations are not fully understood.
Purpose of the Study:
- To compare the responsiveness of elicited peritoneal macrophage subpopulations to bradykinin.
- To investigate the role of the bradykinin B2 receptor in macrophage activation.
- To assess bradykinin's effect on resident alveolar macrophages.
Main Methods:
- Elicited peritoneal macrophages and resident alveolar macrophages from guinea pigs were used.
- Bradykinin-induced secretion of superoxide radical, arachidonic acid, and prostaglandin E2 (PGE2) was measured.
- Bradykinin B2 receptor antagonist (HOE 140) and cyclooxygenase inhibitor (indomethacin) were employed.
- Intracellular calcium ([Ca2+]i) levels were measured to assess receptor activity.
Main Results:
- Bradykinin stimulated peritoneal macrophages via the B2 receptor, inducing secretion of inflammatory mediators.
- Secretion levels varied significantly with macrophage size; intermediate-sized cells showed highest activity, large cells showed minimal activity.
- Bradykinin-stimulated cyclooxygenase products inhibited NADPH-oxidase activity, dependent on macrophage size and activation state.
- Resident alveolar macrophages expressed B2 receptors but showed very low activity compared to peritoneal macrophages.
Conclusions:
- Macrophage differentiation, maturation, and activation stages significantly influence their responsiveness to bradykinin.
- Size-dependent variations in secretory capacity exist within elicited peritoneal macrophage populations.
- Resident alveolar macrophages are less responsive to bradykinin compared to elicited peritoneal macrophages.