Margination and emigration of leucocytes.

A recurrent conclusion of studies on margination and emigration of leucocytes into acute inflammatory lesions has been that these two processes are the result of different stimuli. The recent description of tachyphylaxis of skin lesions to neutrophil chemotaxins is compared with the purported regulation of acute inflammation by deactivation of neutrophils, inactivation of chemotaxins and inhibition of cell migration. It is concluded that tachyphylaxis might regulate the intensity of the peak neutrophil influx whereas chemotaxin inactivators and migration inhibition factors might regulate the subsequent low grade neutrophil influx into lesions. It is suggested that the chemotaxin receptors which manifest tachyphylaxis may be located on endothelial cells of post-capillary venules. The literature indicates that an alteration in endothelium provides a sufficient stimulus for margination to occur. It is emphasised that attention should be directed towards determining the minimal changes in endothelium necessary to permit or induce margination to proceed. Emigration of marginated neutrophils might then occur in response to chemotaxin diffusing to the vessel wall or by locomotion along a gradient of substratum-bound chemotaxin. The selectivity of the leucocyte infiltration of tissues that occurs in some types of inflammation could be exerted by the stimulus for margination or the stimulus for emigration. It is noted that selective margination of lymphocytes occurs in post-capillary venules of lymphoid tissues. The role of a lymphocyte chemotaxin as the stimulus for emigration in this location is unknown. To encompass the known phenomena, a general theory of leucocyte margination and emigration would predict that leucocytes selectively marginate onto acceptor molecules expressed by endothelium and extravasate in response to a chemotactic stimulus. Endothelium-bound chemotaxins may function as acceptor molecules. A bipartisan model of leucocyte migration to extravascular locations is proposed which contends that leucocyte can be recruited non-specifically as inflammatory cells or they can be recruited specifically as effector cells of immune reactions. It is suggested that tachyphylaxis is a characteristic of inflammatory cell recruitment but not of immunologically driven cell recruitment. The binding of chemotaxins to endothelial cells in vivo, the selectivity of margination, the status of margination in desensitised tissues and the role of chemotaxins in lymphocyte recirculation through lymph nodes are identified as critical questions to resolve the mechanisms of leucocyte margination and emigration.