Microvascular mechanisms of histamine-induced potentiation of leukocyte adhesion evoked by chemoattractants

Abstract

1. Intravital microscopy of the rat mesentery was used to examine interactions between histamine and the chemoattractant leukotriene B4 (LTB4) with regard to leukocyte adhesion in postcapillary venules. 2. Topical administration of histamine caused a four fold potentiation of LTB4-induced leukocyte adhesion. 3. Histamine significantly increased the rolling leukocyte flux by 25%, and this effect of histamine on rolling was strictly blood flow-dependent, i.e. we found significant positive correlations between both blood flow and total leukocyte flux and between total and rolling leukocyte flux, while no changes in leukocyte rolling fraction or rolling velocity were observed. Furthermore, histamine caused a clear-cut increase in venular plasma protein leakage. 4. The platelet-activating factor (PAF) receptor antagonist WEB 2086, which effectively inhibited adhesion of leukocytes evoked by exogenous PAF, did not reduce the potentiating effect of histamine on LTB4-induced leukocyte adhesion. 5. The vasodilator acetylcholine (ACh) caused a moderate enhancement of LTB4 induced leukocyte adhesion in proportion to its blood flow-dependent 40% increase in rolling leukocyte flux. In contrast to histamine, ACh did not provoke vascular leakage of plasma proteins. 6. Taken together, our findings suggest that histamine plays an important pro-inflammatory role in tissues where leukocyte rolling is already present, by potentiating chemoattractant-induced firm leukocyte adhesion through a combination of microcirculatory changes such as increased rolling leukocyte flux and vascular permeability.