Mechanisms of mediator release from neutrophils

The encounter of neutrophils with immune complexes and complement components - in the bulk phase or on a surface - leads to their secretion of lysosomal hydrolases, especially neutral proteases, which provoke tissue injury. Secretion of lysosomal enzymes and generation of reactive oxygen species (e.g., O2-. generation are stimulus-specific and can be dissected to establish cause and effect relationships by means of: a) kinetic analysis, b) variations in the stimulus, and c) use of impermeant reagents to block discrete responses. Neutrophils also generate products of 11-cyclooxygenase (e.g., PGE2, TxA2) and of the 5- and 15-lipoxygenases (mono-, di-, and tri-HETEs, LTB4, and their isomers). But the cyclooxygenase products (save TxA2) are not phlogistic by themselves: they inhibit the functions of neutrophils, platelets, macrophages, and mast cells. The most potent pro-inflammatory agent yet identified as a product of arachidonate is LTB4. LTB4 is a potent Ca ionophore, constricts airways, is a potent chemoattractant, and induces local inflammation.