Local histamine release increases leukocyte rolling in the cerebral microcirculation of the mouse

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 sponta neous leukocyte rolling was observed only in the SJL/J strain of mice, and could be prevented by pre surgical 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.