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Local histamine release increases leukocyte rolling in the cerebral microcirculation of the mouse
T Yong1, M Q Zheng, D S Linthicum
1Department of Medical Physiology, Texas A&M University, College Station 77843, USA.
Abstract:
Histamine-mediated induction of leukocyte rolling and adhesion in the cerebral microcirculation was examined in two inbred strains of mice (SJL/J and BALB/c). A cranial window was surgically prepared for the visualization of the cerebral microcirculation using intra-vital microscopy. Leukocyte rolling and adhesion to pial venular walls were assessed during off-line video playback analyses. The surgical preparation of the cranial windows was found to trigger 'spontaneous' leukocyte rolling, and this was attributed to disruption of dural mast cells and localized release of vasoactive histamine. This spontaneous leukocyte rolling was observed only in the SJL/J strain of mice, and could be prevented by presurgical treatment with the mast cell stabilizer sodium cromoglycate. BALB/c mice did not show 'spontaneous' leukocyte rolling or adhesion; this strain is known to have low numbers of CNS-associated mast cells. Exogenous histamine, applied topically to the cerebral microcirculation via the cranial window in mice pretreated with sodium cromoglycate, produced significant dose-dependent increases in leukocyte rolling and adhesion to pial venules in SJL/J mice, but not in BALB/c mice. Diphenhydramine (H1 receptor antagonist), but not cimetidine (H2 receptor antagonist), abolished both 'spontaneous' and histamine-induced leukocyte rolling. Anti-P-selectin antibody was found efficiently to block both spontaneous and histamine-induced increases in leukocyte rolling, but not leukocyte adhesion.
Insights
Histamine causes leukocyte rolling in mouse brain microcirculation, particularly in SJL/J mice, via H1 receptors. This effect is linked to mast cells and P-selectin, impacting neuroinflammation research.
Area of Science:
- Neuroscience
- Immunology
- Microcirculation Research
Background:
- Leukocyte rolling and adhesion are key inflammatory processes.
- Histamine's role in cerebral microcirculation inflammation is not fully understood.
- Mast cells and their mediators, like histamine, are implicated in neuroinflammation.
Purpose of the Study:
- To investigate histamine-mediated leukocyte rolling and adhesion in mouse cerebral microcirculation.
- To compare responses between SJL/J and BALB/c mouse strains.
- To elucidate the receptors and mechanisms involved in histamine-induced leukocyte behavior.
Main Methods:
- Intra-vital microscopy of cerebral microcirculation via cranial window in mice.
- Assessment of leukocyte rolling and adhesion.
- Pharmacological blockade using diphenhydramine (H1 antagonist), cimetidine (H2 antagonist), and anti-P-selectin antibody.
- Mast cell stabilization with sodium cromoglycate.
Main Results:
- SJL/J mice exhibited spontaneous leukocyte rolling post-surgery, linked to mast cell disruption and histamine release, preventable by sodium cromoglycate.
- BALB/c mice, with fewer CNS mast cells, showed no spontaneous rolling.
- Exogenous histamine increased leukocyte rolling and adhesion in SJL/J mice but not BALB/c mice.
- H1 receptor antagonist (diphenhydramine) blocked rolling; H2 antagonist (cimetidine) did not.
- Anti-P-selectin antibody blocked rolling but not adhesion.
Conclusions:
- Histamine, acting via H1 receptors and P-selectin, significantly contributes to leukocyte rolling in the cerebral microcirculation of SJL/J mice.
- Mast cell activation and subsequent histamine release play a critical role in this response.
- Differences between mouse strains highlight the importance of mast cell presence in neuroinflammatory responses.