Molecular control of leukocyte migration

Clare Lloyd,

Leukocyte Biology, Imperial College, London.

One of the characteristic features of the asthmatic reaction is the accumulation of leukocytes within the lung. These leukocytic infiltrates are composed of a variety of different cells of the immune system but eosinophils and lymphocytes are most prevalent. Their accumulation in the lung necessitates their travel from the peripheral circulation, through the vascular endothelium, through the lung parenchymal areas, and ultimately, via the bronchial epithelium to the bronchiolar spaces. This journey involves the complex interplay of a series of molecules that mediate migration to the sites of inflammation. The chemokines and their receptors are thought to be integral to the development of allergic inflammation by mediating recruitment of populations of leukocytes to the lung. In particular the differential expression of chemokine receptors on Th2 cells has been postulated to provide a mechanism by which these cells are selectively recruited to the lung during allergic inflammatory reactions. Th2 cells are central to the initiation and development of pulmonary inflammation after allergen challenge. This is complicated by the finding that multiple chemokines with partially overlapping functions are expressed in the allergic lung, and understanding the individual contributions of key chemokines has been the subject of intense investigation. Mouse models have been utilised to determine the pathophysiological effects of blocking or genetically deleting key chemokines or their receptors. The effects of these studies will be discussed.