Leucocyte attachment

The BBB consists principally of concentric layers of endothelial cells, pericytes, basal membranes, and tightly apposed astrocytic end-feet,7 but it is the endothelium that is predominantly responsible for restricting the entry of leucocytes into the CNS. Several features of the CNS endothelium may contribute to its unique barrier function the cells are interconnected by tight junctions, are relatively devoid of pinocy-totic vesicles and fenestrations, cany an unusually high net negative surface charge,24 and have a low or inappropriate expression of surface adhesion molecules that support leucocyte attachment.21 25"27 Of the small number of leucocytes present in the normal brain, the majority are lymphocytes.3 When the BBB is compromised serious pathological manifestations may ensue as illustrated by multiple sclerosis (MS) in which the features of encephalomyelitis are attributed to the CNS entry, perivascular sequestration, and local activation of sensitized lymphocytes and other blood mononuclear leucocytes. 

Sheridan et al. (1996) used intravital microscopy to record and quantified leucocyte attachment to coronary microvascular endothehum during ischaemia-reperfusion in the beating dog heart and think it likely that activation and attachment of leucocytes promote endothelial injury and represent the initial step to diapedesis and invasion of the myocardium. 

Cl, C2...C9 The 9 main components of complement Cl inhibitor A serine protease inhibitor which inactivates Clr/Cls Clq Complement fragment Iq ClqR Receptor for Clw facilitates attachment of immune complexes to mononuclear leucocytes and endothelium... 

The interaction of the various aP integrin complexes with ICAMs results in firm attachment and spreading. Subsequent VCAM-1-integrin and PECAM-1-integrin interactions are involved in leucocyte transmigration through endothelial cell junctions into the extravascular space. Leucocytes can thence proceed to interact with target cells and initiate inflammatory processes. 

In summary, the process of leucocyte extravasation, from initial attachment to endothelium to the final entry into the surrounding tissue, involves the sequential utilisation of an array of cell surface adhesion molecules. The important features of these adhesion molecules are that whilst some are constitutively expressed, others are induced, upregulated, or converted to a fully functional form only upon activation of endothelial cells or leucocytes. At present, it is not clear whether the arrival of distinct populations of blood leucocytes to an inflammatory lesion depends upon an initial recognition on the endothelial surface of a combination of known adhesion... 

Fig. 304. Attachment of a leucocyte to an interendothelial junction from the interventricular septum (block 1461) of a rat (No. 15) treated for 8 consecutive days with intraperito-neal injection of 15 mg carbocromene per kg body weightx-day. On the last 5 days of experimentation the animal was exposed to an atmosphere containing only 5% oxygen for 30 min. On August 6, 1976 under pentobarbital anaesthesia, the animal was perfused from the abdominal aorta with 2.5 % glutarddehyde in 0.1 M sodium cacodylate buffer. Postfixa-tion with 1 % osmium tetroxide in sodium cacodylate buffer. Embedded in Epon 812 and sectioned at 50 nm. Lead citrate and uranyl acetate. Film 623-01...

Natalizumah (Tysabri ) is used to treat relapsing multiple sclerosis by targeting an integrin protein which enables leucocytes, which are a factor in the disease, to attach themselves to cell surfaces. 

---