Neutrophil function as related to neutrophil-endothelial cell interactions.

Advances have recently been made in several areas related to neutrophil-mediated tissue damage. Certain chemotactic receptors have been cloned, their relationship to G proteins examined, and their mechanisms of downregulation partly elucidated. Downregulation of chemotactic receptors could be useful in controlling the damage inflicted by neutrophils on nearby tissues. Studies of neutrophil adhesion to endothelium have revealed two classes of adhesion proteins: selectins, and the integrin/integrin receptor system. Selectins are involved in neutrophil margination, while the integrin system participates in the egress of neutrophils into regions of inflammation. The microfilaments are strands of polymerized actin which form a network that pervades the neutrophil cytoplasm. On activation of the neutrophil, changes occur in the state of the microfilament network that appear to act in combination with the integrin/integrin receptor system to cause neutrophils to be retained in capillaries of tissues reperfused after hypoxia. To the extent that reperfusion injury is caused by these retained neutrophils, prevention of their effect may require measures directed at the microfilament network as well as the integrin/integrin receptor system. With regard to mechanisms of neutrophil-mediated tissue damage, recent studies have emphasized the extent to which oxidative systems interact with proteases to augment the damage inflicted by activated neutrophils. The unique efficacy of secretory leukoprotease in preventing neutrophil-mediated proteolysis is discussed.