Influence of local haemodynamics on leucocyte rolling and chemoattractant-induced firm adhesion in microvessels of the rat mesentery.

Tissue hyperaemia, oedema formation and leucocyte accumulation are characteristic features of the inflammatory process referable to changes at the microcirculatory level. Here, we used intravital fluorescence video microscopy to assess relationships among haemodynamical parameters, leucocyte rolling, and chemoattractant-induced firm adhesion in small venules (13-24 microM) of the rat mesentery. The rolling leucocyte flux in these vessels was directly proportional to the total leucocyte flux (r = 0.76, P < 0.001), which in turn closely correlated to the venular blood flow (r = 0.77, P < 0.001). Consequently, the rolling to total leucocyte flux fraction, averaging 39 +/- 15%, did not vary with the blood flow and showed no correlation to either blood flow velocity (r = -0.15, P = 0.42) or wall shear rate (r = -0.06, P = 0.77), indicating that the extent of leucocyte rolling is not primarily dependent on the fluid viscous drag at physiological blood flow rates in vivo. Stimulation of the mesentery with the chemoattractant fMLP (10(-6) M) induced firm adhesion of rolling leucocytes. It was found that the number of adherent leucocytes in individual vessels was directly related to the rolling leucocyte flux (r = 0.78, P < 0.001) and hence to the venular blood flow (r = 0.47, P < 0.05), while there was no correlation to the wall shear rate (r = 0.27, P = 0.24). The dependence of the firm adhesive response on the blood flow level and the delivery rate of leucocytes was confirmed at the whole organ level. Thus, leucocyte accumulation in rat skin lesions was markedly enhanced when a vasodilator was co-administered with the chemotactic stimulus compared with chemotactic stimulation alone. The data indicate that, within a physiological blood flow range, the leucocyte response to chemotactic stimulation is largely independent of the prevailing hydrodynamic shear forces. Instead, manifestation of the firm adhesive response, because of its dependence on the preceding rolling interaction, is clearly related to the blood flow level in the microvessels, which emphasizes the significance of tissue hyperaemia in inflammation.