Mouse pancreatic islet macrophages use locally released ATP to monitor beta cell activity
| Autor: | Madina Makhmutova, Rayner Rodriguez-Diaz, Jonathan Weitz, Alejandro Caicedo, Kristie Aamodt, Joana Almaça, Stephan Speier, Marcela Brissova, Julia Stertmann |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Endocrinology Diabetes and Metabolism Stimulation Enteroendocrine cell Biology Article 03 medical and health sciences Islets of Langerhans Mice 0302 clinical medicine Adenosine Triphosphate Internal medicine Insulin-Secreting Cells Internal Medicine medicine Animals Insulin Secretion Pancreas Atp Beta Cell Calcium Imaging Macrophage Purinergic Tissue Slice geography geography.geographical_feature_category Pancreatic islets Macrophages Purinergic receptor Islet Cell biology 030104 developmental biology medicine.anatomical_structure Endocrinology Beta cell 030217 neurology & neurosurgery |
| Zdroj: | Diabetologia 61, 182–192 (2018) |
| ISSN: | 1432-0428 |
| Popis: | 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 Ca 2+ 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink