Chemokines act as ligands for the chemokine
Chemokines act as ligands for the chemokine receptors, which possess 7-transmembran domain-type proteins functionally coupled to G proteins. Leukocytes express 19 chemokine receptors which control their influx and activation at the site of inflammation. Human neutrophils express both CXCR-1 and CXCR-2 chemokine receptors consisting of approximately 350 amino acids, which is a high degree of sequence homology. Because of this similarity, their some functions are the same. For instance, stimulation of both receptors by specific chemokine ligands could activate the leukocytes for migration. However, there is some functional dissimilarity between two receptors. For example, IL-8 and GCP-2 stimulate both CXCR-1 and CXCR-2 chemokine receptor although GRO-alpha and ENA-78 could activate only CXCR-2. Previous studies have suggested that β1 integrins are more involved than β2 integrins in migration of neutrophils through extracellular matrix . It was recently demonstrated that the tail of CXCR-1 chemokine receptor was responsible for β1 integrin-dependent cell migration stimulated by IL-8 in mononuclear cell lines . Furthermore, CXCR-2 chemokine receptor were expressed in endothelial cells, and associated with angiogenesis induced by ELR (+) CXC chemokine as mentioned above , .
Neutrophils across to synovial fluid in inflammatory arthritides and contribute to tissue damage by releasing their Cinacalcet HCl mg and producing reactive oxygen species (ROS). Both the beneficial and harmful roles of neutrophils are critically dependent on the capacity of the cell to undergo directed migration from the blood into local tissue sites. Chemokines and chemokine receptors play a major role in this migration process. We recently reported that ELR (+) CXC chemokines IL-8, GRO-α, ENA-78 and GCP-2 were much more abundantly secreted into synovial fluid of patients with rheumatoid arthritis (RA) than those with osteoarthritis (OA), Behçet\'s disease (BD) and Familial Mediterranean fever (FMF), in which last two are characterized by non-erosive arthritis, and proposed that those chemokines might be associated with erosive changes .
Discussion An important characteristic of the early phase of inflammatory response is the migration of neutrophils to the site of inflammation in response to chemokines and several chemoattractants. Later in the course, chronic inflammatory process begins as a result of cellular infiltration which predominantly consists of lymphocytes . It has been well known that RA is characterized by chronic synovitis even at an earlier stage of the illness and synovitis can be observed before the onset clinical findings . Although the synovitis of RA has features which are representative of chronic inflammation with respect to the type of the cellular infiltrate, RA is regarded as a prototype of diseases characterized by neutrophilic inflammation. High amounts of neutrophils are found in synovial fluid of patients with RA. Furthermore, their proteases and enzymes also contribute to the destruction of cartilage and related joint structures. Several studies have shown the involvement of ELR (+) CXC chemokines (IL-8, GRO-α, GCP-2, ENA-78) in the ingress of neutrophils into synovial tissue and fluid in RA , , , , . We have recently investigated synovial levels of IL-8, GRO-α, GCP-2, and ENA-78 in patients with RA, OA, FMF, and BD and found marked increase in the synovial levels of all these markers in patients with RA as compared to others . Synovial IL-8 levels were found to be elevated more strikingly in patients with RA. In the light of these findings, we suggested that CXC chemokines can contribute to the erosive changes seen in RA by causing migration of neutrophils into the synovial fluid and their long lasting accumulation within the synovium. We also proposed that angiogenic properties of these cytokines might play an important role during the course of chronic inflammation.