Neutrophil Specific Granule Deficiency

Abstract

Neutrophil specific granules are thought to be important in the evolution of the inflammatory response. Specific granules are preferentially released with minor membrane perturbation in vitro or in vivo, and secreted products probably have important effects on humoral and cellular components of inflammation. In vitro studies reveal that some secreted specific granule products activate the complement cascade to generate the chemoattractant C5a and the opsonin C3b, while other secreted products are selectively chemotactic for monocytes. Translocation of receptors for chemoattractants (fmet-leu-phe) and opsonins (C3bi) from specific granules or closely related organelles to the plasma membrane may play an important role in chemotaxis, adherence, and phagocytosis. Similar translocation of constituents of the electron transport chain involved in the respiratory burst (i.e. cytochrome b) probably plays a role in neutrophil oxidative metabolism and hydrogen peroxide generation. In vivo and in vitro studies of neutrophils from patients with congenital specific granule deficiency, acquired specific granule deficiency (thermal injury and neonates), or normal neutrophils experimentally depleted of nuclei and organelles support these conclusions. Thus, release of specific granule constituents appears to be important for amplification of the initial and subsequent phases of the inflammatory response.

Rapid Neutrophil Response Controls Fast‐Replicating Intracellular Bacteria but Not Slow‐ReplicatingMycobacterium tuberculosis

“…Neutropenic patients reflect a more chronic neutropenia than do mice experimentally depleted of neutrophils. Nevertheless, patients mainly are infected with fastreplicating bacteria and fungi [11,[51][52][53]55]. Few reports described infection of neutropenic patients with M. fortuitum, which may reflect our observation of increased M. fortuitum burden in the lung of neutrophil-depleted mice.…”

“…Neutropenia can result from exposure to x-rays or chemotherapy or can result from inherited genetic defects [11,[50][51][52][53][54]. Neutropenic patients reflect a more chronic neutropenia than do mice experimentally depleted of neutrophils.…”

“…As one of the most efficient phagocytic cells of the immune system, neutrophils restrict the initial, local replication of numerous pathogens and thereby delay their systemic spread. Second, neutrophils release an array of cytokines and chemokines and attract other cells of the innate as well as the acquired immune system [7][8][9][10][11]. Neutrophils therefore not only contribute to immediate pathogen restriction but also focus the specific immune response to the site of infection, which ultimately achieves control of the pathogen.…”

Neutrophil degranulation inhibits potential hydroxyl-radical formation. Relative impact of myeloperoxidase and lactoferrin release on hydroxyl-radical production by iron-supplemented neutrophils assessed by spin-trapping techniques

“…Studies in vitro of neutrophils obtained from the small number of patients with specificgranule (LF) deficiency have revealed multiple abnormalities [68]. The role of LF in the recurrent infections noted in those patients is unclear.…”

Enhanced Expression of the Eosinophil-derived Neurotoxin Ribonuclease (RNS2) Gene Requires Interaction between the Promoter and Intron

“…In addition, a 15-base pair segment that is identical to a sequence found in the 5Ј promoter region of the neutrophil-specific granule protein, lactoferrin (24), is highlighted. The coordinate control of eosinophil and neutrophil granule protein biosynthesis was suggested by a series of studies examining the rare genetic disorder known as neutrophil specific granule deficiency (28,29). Lomax and colleagues (30) determined that the defective biosynthesis of lactoferrin observed in this disorder resulted from a defect in mRNA transcription affecting specifically cells of the neutrophil lineage.…”