Polymorphonuclear leukocytes as secretory organs of inflammation

Abstract

Polymorphonuclear (PMN) leukocytes mediate that phase of inflammation at which vascular responses become translated into tissue injury. After phagocytosis, the PMN leukocyte generates derivatives of molecular oxygen (O2-.,OH., and H2O2) that stimulate a metabolic burst and assist in the killing of microorganisms. They also release oxidation products of membrane fatty acids (e.g., arachidonate), which are detected as thromboxanes and protaglandins. After interaction of phagocytic ligands (immune complexes and C3b-opsonized particles), the PMN leukocyte secretes lysosomal enzymes from open phagocytic vacuoles, and, especially when phagocytosis is blocked by cytochalasin B, secretes them directly into the cell's surrounding fluids. Secretion is enhanced by agents that elevate intracellular levels of cyclic GMP, and inhibited by agents that raise cyclic AMP. These reciprocal changes are associated with assembly and disassembly (respectively) of cytoplasmic microtubules. These cytoskeletal structures, together with contractile elements, regulate in part the secretory events of inflammation in which lysosomal constituents (e.g., elastase, collagenase, and cathepsin G) are diverted from their intracellular depots to an inappropriate assault on the tissues of the host.