Leukocyte chemoattractants

A variety of molecules (chemoattractants) stimulate the directed migration of immune cells. Leukocyte chemoattractants may be generated at inflammatory sites or as a consequence of immune cell interactions and may serve to regulate the directed recruitment of specific leukocyte subsets to inflammatory foci in vivo. Some of the most potent leukocyte chemoattractants are summarized in Table 1. Neutrophils and monocytes share chemotactic responsiveness to several chemoattractants, including a cleavage product of the fifth component of complement (C5a), synthetic N-formyl-methionyl peptides which are structurally similar to N-formyl peptides generated by bacteria, arachidonic acid lipoxygenation metabolites such as leukotriene B4 and platelet-activating factor.

Numerous secreted proteins of approximately 7090 amino acids in length have been identified as chemokines. Some chemokines are generated consti-tutively; however, most chemokines act as second ary cell activation signals during inflammatory responses. Chemokines have been divided into three groups (C, C-C and C-X-C) based on the number and arrangement of cysteines. The C chemokines have two cysteines. The C-C and C-X-C chemokines have four cysteines and are distinguished by the presence (C-X-C) or absence (C-C) of a single amino acid between the first and second cysteines. Cysteines 1 and 3 and cysteins 2 and 4 form disulfide bonds in C-C and C-X-C chemokines. The chemokines exhibit 20-30% amino acid sequence identity across groups and can be substantially more conserved within groups.

Examples of selected chemokines and their responding cell types are provided in Table 1. Only one C chemokine, lymphotactin, has been identified, whereas more than a dozen each of C-C and C-X-C chemokines have been discovered. The chemokines exhibit specificity for leukocyte types. The C-X-C. chemokines predominantly attract neutrophils; however, lymphotactin and most C-C chemokines do not. Most C-C chemokines attract monocytes, whereas lymphotactin and C-X-C chemokines do not. One C-C chemokine, MIP-la,ß, attracts neutrophils, eosinophils, basophils, monocytes and T lymphocytes. The other C-C chemokines do not stimulate neutrophil migration. A chemokine distantly related to C-X-C and C-C chemokines, SDF-1, exhibits a broad spectrum of activity, attracting neutrophils, monocytes and T lymphocytes. SDF-1 is the most active T lymphocyte chemoattractant thus far identified and is also a potent stromal cell-derived preß cell growth-stimulating factor.

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