Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils.

Introduction Neutrophil accumulation in a tissue is characteristic of inflammation and is observed in a variety of pathological conditions as disparate as infection, trauma, ischemia, and cancer. The process of tissue infiltration is best understood in bacterial infection, where neutrophils are selectively attracted in large numbers to phagocytose and kill the invaders. In other conditions neutrophils are presumably recruited as scavengers of damaged tissue or unwanted extracellular deposits like immune complexes or fibrin. Phagocytosis is accompanied by the release of granule enzymes, superoxide, H202, and a variety of bioactive lipids. Several of these products are required for the killing and digestion of microorganisms. They also induce inflammation and tissue damage, however, which is normally observed after neutrophil accumulation. Several neutrophil chemoattractants have been characterized in recent years; the best known are the anaphylatoxin C5a (1), formylmethionyl peptides of bacterial origin (2), plateletactivating factor (PAF; 3),1 and leukotriene B4 (LTB4; 4). These stimuli have different origins and modes of formation, and their occurrence in disease must thus be expected to vary in accord with the underlying pathophysiological process. C5a is formed upon complement activation via the classical pathway after interaction of microorganisms with antibodies or the formation of immune complexes, or via the alternative pathway after the nonimmune recognition of foreign materials. In bacterial infections, on the other hand, formylmethionyl peptides (which are released by the microorganisms) are likely to be the major attractants. PAFand LTB4 are of special interest because they can be generated by the neutrophils themselves and may thus function as autoor paracrine amplifiers of the responses elicited by other stimuli (5). It has been shown that CSa, formylmethionyl peptides, PAF, and LTB4 act via unrelated receptors, suggesting that neutrophil recruitment can result from the concerted action of multiple stimuli.