MICROVASCULAR MECHANISMS OF HISTAMINE-INDUCED POTENTIATION OF LEUKOCYTE ADHESION EVOKED BY CHEMOATTRACTANTS

1 Intravital microscopy of the rat mesentery was used to examine inter actions between histamine and the chemoattractant leukotriene B-4 (LTB (4)) with regard to leukocyte adhesion in postcapillary venules. 2 Top ical administration of histamine caused a four fold potentiation of LT B(4)-induced leukocyte adhesion. 3 Histamine significantly increased t he rolling leukocyte flux by 25%, and this effect of histamine on roll ing was strictly blood flow-dependent, i.e. we found significant posit ive correlations between both blood flow and total leukocyte flux and between total and rolling leukocyte flux, while no changes in leukocyt e rolling fraction or rolling velocity were observed. Furthermore, his tamine caused a clear-cut increase in venular plasma protein leakage. 4 The platelet-activating factor (PAF) receptor antagonist WEB 2086, w hich effectively inhibited adhesion of leukocytes evoked by exogenous PAF, did not reduce the potentiating effect of histamine on LTB(4)-ind uced leukocyte adhesion.5 The vasodilator acetylcholine (ACh) caused a moderate enhancement of LTB(4)-induced leukocyte adhesion in proporti on to its blood flow-dependent 40% increase in rolling leukocyte flux. In contrast to histamine, ACh did not provoke vascular leakage of pla sma proteins. 6 Taken together, our findings suggest that histamine pl ays an important pro-inflammatory role in tissues where leukocyte roll ing is already present, by potentiating chemoattractant-induced firm l eukocyte adhesion through a combination of microcirculatory changes su ch as increased rolling leukocyte flux and vascular permeability.