The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus
Neuroinflammation contributes to or even causes central nervous system (CNS) diseases, and its regulation is thus crucial for brain disorders. Mast cells (MCs) and microglia, two resident immune cells in the brain, together with astrocytes, play critical roles in the progression of neuroinflammation...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/8098439 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832566117323767808 |
|---|---|
| author | Yiwei Wang Huanhuan Sha Leting Zhou Yinan Chen Qin Zhou Hongquan Dong Yanning Qian |
| author_facet | Yiwei Wang Huanhuan Sha Leting Zhou Yinan Chen Qin Zhou Hongquan Dong Yanning Qian |
| author_sort | Yiwei Wang |
| collection | DOAJ |
| description | Neuroinflammation contributes to or even causes central nervous system (CNS) diseases, and its regulation is thus crucial for brain disorders. Mast cells (MCs) and microglia, two resident immune cells in the brain, together with astrocytes, play critical roles in the progression of neuroinflammation-related diseases. MCs have been demonstrated as one of the fastest responders, and they release prestored and newly synthesized mediators including histamine, β-tryptase, and heparin. However, temporal changes in MC activation in this inflammation process remain unclear. This study demonstrated that MC activation began at 2 h and peaked at 4 h after lipopolysaccharide (LPS) administration. The number of activated MCs remained elevated until 24 h after LPS administration. In addition, the levels of histamine and β-tryptase in the hippocampus markedly and rapidly increased within 6 h and remained higher than the baseline level within 24 h after LPS challenge. Furthermore, mast cell-deficient KitW-sh/W-sh mice were used to investigate the effects of MCs on microglial and astrocytic activation and blood-brain barrier (BBB) permeability at 4 h after LPS stimulation. Notably, LPS-induced proinflammatory cytokine secretion, microglial activation, and BBB damage were inhibited in KitW-sh/W-sh mice. However, no detectable astrocytic changes were found in WT and KitW-sh/W-sh mice at 4 h after LPS stimulation. Our findings indicate that MC activation precedes CNS inflammation and suggest that MCs are among the earliest participants in the neuroinflammation-initiating events. |
| format | Article |
| id | doaj-art-28a250dab7d343eca98b7b15b70cf2ed |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-28a250dab7d343eca98b7b15b70cf2ed2025-02-03T01:05:03ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/80984398098439The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the HippocampusYiwei Wang0Huanhuan Sha1Leting Zhou2Yinan Chen3Qin Zhou4Hongquan Dong5Yanning Qian6Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, ChinaThe First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaWuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, ChinaThe First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaJiangsu Cancer Hospital, Nanjing, Jiangsu, ChinaThe First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaThe First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, ChinaNeuroinflammation contributes to or even causes central nervous system (CNS) diseases, and its regulation is thus crucial for brain disorders. Mast cells (MCs) and microglia, two resident immune cells in the brain, together with astrocytes, play critical roles in the progression of neuroinflammation-related diseases. MCs have been demonstrated as one of the fastest responders, and they release prestored and newly synthesized mediators including histamine, β-tryptase, and heparin. However, temporal changes in MC activation in this inflammation process remain unclear. This study demonstrated that MC activation began at 2 h and peaked at 4 h after lipopolysaccharide (LPS) administration. The number of activated MCs remained elevated until 24 h after LPS administration. In addition, the levels of histamine and β-tryptase in the hippocampus markedly and rapidly increased within 6 h and remained higher than the baseline level within 24 h after LPS challenge. Furthermore, mast cell-deficient KitW-sh/W-sh mice were used to investigate the effects of MCs on microglial and astrocytic activation and blood-brain barrier (BBB) permeability at 4 h after LPS stimulation. Notably, LPS-induced proinflammatory cytokine secretion, microglial activation, and BBB damage were inhibited in KitW-sh/W-sh mice. However, no detectable astrocytic changes were found in WT and KitW-sh/W-sh mice at 4 h after LPS stimulation. Our findings indicate that MC activation precedes CNS inflammation and suggest that MCs are among the earliest participants in the neuroinflammation-initiating events.http://dx.doi.org/10.1155/2020/8098439 |
| spellingShingle | Yiwei Wang Huanhuan Sha Leting Zhou Yinan Chen Qin Zhou Hongquan Dong Yanning Qian The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus Mediators of Inflammation |
| title | The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus |
| title_full | The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus |
| title_fullStr | The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus |
| title_full_unstemmed | The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus |
| title_short | The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus |
| title_sort | mast cell is an early activator of lipopolysaccharide induced neuroinflammation and blood brain barrier dysfunction in the hippocampus |
| url | http://dx.doi.org/10.1155/2020/8098439 |
| work_keys_str_mv | AT yiweiwang themastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT huanhuansha themastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT letingzhou themastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT yinanchen themastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT qinzhou themastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT hongquandong themastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT yanningqian themastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT yiweiwang mastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT huanhuansha mastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT letingzhou mastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT yinanchen mastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT qinzhou mastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT hongquandong mastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus AT yanningqian mastcellisanearlyactivatoroflipopolysaccharideinducedneuroinflammationandbloodbrainbarrierdysfunctioninthehippocampus |