Defective bactericidal activity and absence of specific granules in neutrophils from a patient with recurrent bacterial infections

Abstract

Recent studies have suggested that specific granules and/or their contents may have a role in neutrophil adherence, oxidative metabolism, and other aspects of cell function. In the current report, we studied neutrophil function in a 13-year-old female with recurrent pyogenic infections and absent specific granules previously documented by electron microscopy. Levels of cobalamin (vitamin B12)-binding protein and lactoferrin were markedly decreased in this patient's neutrophils. Bactericidal activity against Escherichia coli was decreased at 60 and 120 min (percentage organisms killed: patient neutrophils, 48 and 33%; control neutrophils, 90 and 99%, respectively). Defective killing of Staphylococcus aureus was also documented. Degranulation and adherence were normal. Levels of lactoferrin and cobalamin-binding protein were decreased in plasma but normal in saliva, indicating that the defect was specific for hematopoietic tissue. Superoxide anion production was normal in the patient, while hydroxyl radical generation was decreased in response to opsonized zymosan. The data support the concept that specific granules and their contents are important for oxidative metabolism and other neutrophil functions.

Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation

“…2). Although total cell myloperoxidase, lysozyme, lactoferrin, and alkaline phosphatase were similar in patient neutrophils compared with those of healthy adult controls (7,8), the patient's neutrophils demonstrated a defect in azurophilic granule release in response to different stimuli. PMA-or fMLP-stimulated release of azurophilic granules (9), as measured by myloperoxidase, was completely absent (Fig.…”

“…Supernatants were removed from the cells after centrifugation and assayed for myeloperoxidase (MPO) and lactoferrin (LF) by using a colorimetric assay and ELISA, respectively (7,8). Total cell content of alkaline phosphatase, lysozyme, MPO, and LF for 10 6 neutrophils was also measured (7)(8)(9). The amount of MPO and LF released into the supernatant was represented as a percentage of total cell content (7)(8)(9).…”

“…Total cell content of alkaline phosphatase, lysozyme, MPO, and LF for 10 6 neutrophils was also measured (7)(8)(9). The amount of MPO and LF released into the supernatant was represented as a percentage of total cell content (7)(8)(9). O 2 Ϫ production by intact neutrophils was measured as superoxide dismutase (SOD)-inhibitable cytochrome c reduction.…”

Infections in Patients with Inherited Defects in Phagocytic Function

“…Skin lesions are often indolent, requiring months to heal. S. aureus is responsible for most infections, and P. aeruginosa is occasionally identified in cases of mastoiditis (12,101,149,265). Candida infections have been seen, but invasive fungal disease has not (46,101,149,215).…”

C/EBPε mediates nicotinamide-enhanced clearance of Staphylococcus aureus in mice

“…For example, the golden pigment of S. aureus is an important virulence factor that shields the pathogen from host oxidative killing, and we have previously shown that blocking the biosynthesis of this pigment could be a strategy for treatment of S. aureus infection (4). Conversely, among human genetic conditions that alter susceptibility to S. aureus infection is neutrophil-specific granule deficiency (SGD), a rare hematologic disorder characterized by a significantly defective immunity (5)(6)(7)(8). Patients with SGD present with functional defects in neutrophils, as well as monocytes/macrophages, and suffer from recurrent life-threatening bacterial infections, including S. aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae.…”