Chapter 7 - Polymorphonuclear cells

Abstract

Neutrophils have been proposed to play important pathogenic roles in systemic lupus erythematosus (SLE). As the most abundant white blood cells in humans, dysregulation in neutrophil biology can promote significant perturbation in immune responses and control of tissue inflammation. Neutrophil can release reactive oxygen species and various bactericidal proteins, diverse proinflammatory cytokines, and form neutrophil extracellular traps (NETs). In SLE, increases in specific neutrophil subsets (low-density granulocytes) lead to myriad aberrant neutrophil-specific responses, including enhanced synthesis of mitochondrial reactive oxygen species, increased formation of NETs, enhanced secretion of proinflammatory cytokines, and accelerated vascular damage. NETs amplify a variety of autoimmune and proinflammatory responses in SLE, including autoantigen externalization, activation of the inflammasome machinery, and dysregulation of innate and adaptive immune responses. These abnormalities contribute to autoantibody production, tissue damage, and vasculopathy. Strategies that target aberrant neutrophil phenotype and function in SLE may contribute to abrogating organ complications and comorbidities in this disease.