Chemotactic factors

Lists of chemotactic factors are given in Tables 1 and 2 under the Chemotaxis article, although there are many others which are not included. Many act on both neutrophils and monocytes/macrophages but not on lymphocytes. These include well-known factors such as C5a, formyl peptides and leukotriene B4. More recently, studies of the chemokine family have shown that a-chemokines such as IL-8 are neutrophil specific, whereas (3-chemokines are monocyte specific, thus providing a mechanism for the specificity of influx of inflammatory cells into different types of lesion.

It is important to emphasize that the term 'chemotactic factor' is inadequate to describe the actions of these factors. In locomotion assays their prime effect is always to stimulate locomotion, and the form the locomotion takes, i.e. whether it is directed or random, depends on whether a gradient is present or not. But as well as effects on locomotion, these factors stimulate various metabolic and microbicidal activities of the cell (Table 1).

Formyl peptides are probably the most widely studied of all chemotactic factors. Formyl-met-leu-phe (FMLP) is the best-studied example but many related peptides have similar actions. They are putative representatives of release products from bacteria. Prokaryotic cells commence protein synthesis with a formyl-methionyl starter sequence which is later cleaved and may be recognized as a leukocyte attract-ant. There are probably many other prokaryotic chemoattractants which have not been defined, as most work has been concentrated on endogenously-derived attractants. The first of the latter to be defined was C5a, a peptide generated by complement activation which probably plays a major role in many inflammatory situations. Leukotriene B4 (LTB4) is generated by neutrophils themselves upon activation, and is likely to act as an amplifying device calling cells into sites of activation. Interest has centered recently on IL-8 and related chemokines, which are present at active concentrations in many inflammatory lesions, including those of rheumatoid arthritis and inflammatory lung disease, and which are produced by macrophages and other types of cells, including epithelial cells and vascular endothelial cells, usually following stimulation of these cells. Other cytokines such as TNFa and granulo-cyte-macrophage colony-stimulating factor (GM-CSF) also have chemoattractant activity for neutrophils. These are just as active as chemokines.

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