Inflammation/inflammatory response leukocyte recruitment

Various adhesion molecules are reported to be expressed on vascular endothelial cells at sites of inflammation (Libby, 2002). In fact, VCAM-1, expressed on the surface of vascular endothelial cells in response to inflammatory stimuli, is suggested to play an important role in leukocyte recruitment (Gerrity et al, 1979). The adhesion of monocytes to vascular endothelial cells is the first critical step in the induction of atherosclerosis (Glass and Witztum, 2001). Supportively, the expression of VCAM-1 is reported to increase in atherosclerosis lesions (Cybulsky and Gimbrone,... 

Inflammation involves various immune-system cells and numerous mediators. Recruitment of blood leukocytes characterizes the initiation of inflammatory response. The migrated or activated immune cells generate and release a variety of mediators that control the progression and resolution of information. Among the numerous inflammatory mediators are cytokines and lipid mediators. 

Although not all inflammatory disorders result in fibrosis, fibrotic responses are always preceded and potentially perpetuated by chronic inflammation. The salient feature of chronic inflammation is the association of leukocyte infiltration. These recruited leukocytes contribute to the pathogenesis of chronic inflammation, and promote fibrosis via the elaboration of a variety of cytokines. The maintenance of leukocyte recruitment during inflammation requires intercellular communication between infiltrating leukocytes and the endothelium, resident stromal cells, and parenchymal cells. These events are mediated via the generation of early response cytokines, e.g., IL-1 and TNF, the expression of cell surface adhesion molecules, and the production of chemotactic molecules, such as chemo-kines. 

There are multicellular interactions that are important in inflammatory processes and in vascular remodeling. Activated platelets induce endothelial cells to secrete chemokines and to express adhesion molecules, indicating that platelets could initiate an inflammatory (Table I) response of the vessel wall. Activated platelets promote leukocyte binding to inflamed or atherosclerotic lesions (27,28). Cell adhesion molecules (CAMs) are responsible for leukocyte-endothelium interactions. It plays a crucial role in inflammation and atherogenesis. Vascular CAM-1 (VCAM-I)and intracellular CAM-1 (ICAM-I) promote monocyte recruitment to sites of injury and constitute a critical step in inflammation and in atherosclerotic plaque development. TSP-1, a matricellular protein released in abundance from activated platelets and accumulated in sites of vascular injury, induces the expression of VCAM-1 and ICAM-1 on endothelium and significantly increases the monocyte attachment (29). 

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