Mouse pancreatic islet macrophages use locally released ATP to monitor beta cell activity
Diabetologia, 2018•Springer
Aims/hypothesis Tissue-resident macrophages sense the microenvironment and respond by
producing signals that act locally to maintain a stable tissue state. It is now known that
pancreatic islets contain their own unique resident macrophages, which have been shown
to promote proliferation of the insulin-secreting beta cell. However, it is unclear how beta
cells communicate with islet-resident macrophages. Here we hypothesised that islet
macrophages sense changes in islet activity by detecting signals derived from beta cells …
producing signals that act locally to maintain a stable tissue state. It is now known that
pancreatic islets contain their own unique resident macrophages, which have been shown
to promote proliferation of the insulin-secreting beta cell. However, it is unclear how beta
cells communicate with islet-resident macrophages. Here we hypothesised that islet
macrophages sense changes in islet activity by detecting signals derived from beta cells …
Aims/hypothesis
Tissue-resident macrophages sense the microenvironment and respond by producing signals that act locally to maintain a stable tissue state. It is now known that pancreatic islets contain their own unique resident macrophages, which have been shown to promote proliferation of the insulin-secreting beta cell. However, it is unclear how beta cells communicate with islet-resident macrophages. Here we hypothesised that islet macrophages sense changes in islet activity by detecting signals derived from beta cells.
Methods
To investigate how islet-resident macrophages respond to cues from the microenvironment, we generated mice expressing a genetically encoded Ca2+ indicator in myeloid cells. We produced living pancreatic slices from these mice and used them to monitor macrophage responses to stimulation of acinar, neural and endocrine cells.
Results
Islet-resident macrophages expressed functional purinergic receptors, making them exquisite sensors of interstitial ATP levels. Indeed, islet-resident macrophages responded selectively to ATP released locally from beta cells that were physiologically activated with high levels of glucose. Because ATP is co-released with insulin and is exclusively secreted by beta cells, the activation of purinergic receptors on resident macrophages facilitates their awareness of beta cell secretory activity.
Conclusions/interpretation
Our results indicate that islet macrophages detect ATP as a proxy signal for the activation state of beta cells. Sensing beta cell activity may allow macrophages to adjust the secretion of factors to promote a stable islet composition and size.
Springer
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