Historical background

In the late nineteenth century, Metchnikoff first suggested that phagocytic leukocytes were important in host defense against infectious pathogens. After noting that leukocytes move toward bacteria and ingest them, he induced local recruitment of macrophages and demonstrated protection of the host against otherwise lethal doses of bacteria. However, Metch-nikoff's concept of recruitment and activation of leukocytes, the cellular theory of immunity, sparked intense opposition from the humoralists who supported the theories advanced by Koch and others for an exclusive role of circulating antibodies in protective immunity. Indeed, proponents of the humoral theory of immunity considered the inflammatory reaction and the accompanying macrophages to be harmful rather than beneficial to the host, setting back the study of cellular mechanisms of immunity for decades.

Not until the 1950s and 1960s did a revival of interest in the mechanisms of cellular recruitment and activation occur as their importance in transplantation, delayed hypersensitivity and immunodeficiency was recognized. Moreover, investigators soon realized that inflammatory cell infiltrates were not merely exudative, but rather dependent on an active migration of leukocytes from the circulation to the site of inflammation. Intense investigation of the mechanisms involved in leukocyte adhesion and recruitment, particularly within the past decade, has revealed that these events are not only very complex, but importantly also provide potential targets for therapeutic intervention.

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