Spontaneous and Fas-mediated apoptosis are diminished in umbilical cord blood neutrophils compared with adult neutrophils

Allgaier, Bernhard; Shi, Min; Luo, Defang; Koenig, Joyce M.

doi:10.1002/jlb.64.3.331

Cited by 49 publications

(71 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1); the proportion of necrotic PMN was Ͻ1% in either population. A greater proportion of cord blood PMN were nonapoptotic (annexin V-negative) after 24 h of culture (35 Ϯ 3%) compared with adult PMN (14 Ϯ 4%, p Ͻ 0.001), similar to differences we previously reported (18). At 24 h, the proportion of necrotic (annexin V-positive/7-AAD-positive) PMN were similar in cord blood (6 Ϯ 5%) and adult (7 Ϯ 2%, p ϭ 0.35) cultures.…”

Section: Resultssupporting

confidence: 89%

“…We previously determined that neonatal PMN have a delay in their onset of spontaneous and Fas-mediated apoptosis in vitro (18). PMN that survive conditions associated with spontaneous apoptosis retain some degree of functionality (9), although whether this applies to neonatal PMN has not been described.…”

mentioning

confidence: 99%

“…In previous in vitro studies, we observed that neonatal PMN had an intrinsic delay in both spontaneous and Fasmediated apoptosis (18), which was associated with decreased activity of caspase-3 (52), a critical downstream mediator of PMN apoptosis (53). Delayed apoptosis and the subsequent survival of PMN leads to their persistence in tissues, because PMN removal by the reticuloendothelial system depends on the recognition of, and ingestion of, apoptotic PMN by resident macrophages (5-7).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Neonatal Neutrophils with Prolonged Survival Exhibit Enhanced Inflammatory and Cytotoxic Responsiveness

et al. 2005

View full text Add to dashboard Cite

Apoptosis is critical to the resolution of inflammation, as it promotes the removal of neutrophils (PMN) by the reticuloendothelial system. In contrast, PMN persistence characterizes the early stages of chronic inflammation. Adult PMN with delayed senescence retain some functionality, although this has not been described for neonatal PMN. We hypothesized that neonatal PMN with prolonged survival retain cytotoxic and inflammatory function. To test one aspect of inflammatory function, we determined surface CD11b expression on 0-h and 24-h PMN after chemotactic formyl-methionine-leucine-phenylalanine (fMLP) stimulation. Although fMLP induced a greater percentage upregulation of CD11b on 0-h adult PMN, this was similar between nonapoptotic cord blood and adult PMN at 24 h. Furthermore, percentage up-regulation of CD11b was more robust for 24-h than for 0-h cord blood PMN. In contrast, there was no difference in responsiveness between 0-h and 24-h adult PMN. In studies of cytotoxic potential, we determined the expression of reactive oxygen intermediates (ROI) in phorbol 12-myristate 13-acetatestimulated cord blood and adult PMN at 0 h and in 24-h nonapoptotic PMN, using the dihydrorhodamine 123 assay.Stimulated cord blood PMN generated more ROI than did adult PMN at both 0 h and 24 h; in addition, ROI levels in 24-h cord blood PMN were similar to those of 0-h adult PMN. We conclude that PMN with prolonged survival retain specific cytotoxic and inflammatory functions, and these are enhanced in cord blood PMN. We speculate that neonatal PMN with prolonged survival have the functional capacity to contribute to the pathogenesis of inflammatory disorders. Abbreviations CLD, chronic lung disease DHR, dihydrorhodamine 123 fMLP, formyl-methionine-leucine-phenylalanine PE, phycoerythrin PMA, phorbol 12-myristate 13-acetate PMN, neutrophil(s) ROI, reactive oxygen intermediates 7-AAD, 7-aminoactinomycin PMN serve as the primary line of host defense during the early stages of sepsis and inflammation (1). After activation by systemic or local factors, primed endothelial cells interact with PMN through adhesion molecules that include selectins and integrins (2). These adhesive interactions initiate a process that allows the extravasation of PMN into inflamed tissue with the goal of neutralizing the inciting stimulus. In the case of inflammation mediated by bacterial or fungal microorganisms, phagocytosis and subsequent killing of these invaders occurs through mechanisms that partly involve ROI and proteases (3,4).The concept that apoptosis of inflammatory PMN and their timely removal by resident macrophages are critical to the resolution of inflammation has been well established (5,6). During the resolution phase, PMN typically undergo the phenotypic changes associated with apoptosis, which promotes their removal by resident macrophages (7). PMN can also undergo necrosis and lysis, a process that induces cytotoxicity in surrounding tissues (8), although apoptosis is the more common and physiologically preferable route. All cells a...

show abstract

Section: Resultssupporting

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Neonatal Neutrophils with Prolonged Survival Exhibit Enhanced Inflammatory and Cytotoxic Responsiveness

et al. 2005

View full text Add to dashboard Cite

show abstract

“…1). In both neonatal cell populations, apoptosis was significantly reduced when compared with adult cells, which is consistent with previous reports (1,2,14). In further studies, we analyzed potential mechanisms underlying the inhibitory effects of labor on neonatal neutrophil apoptosis.…”

Section: Resultssupporting

confidence: 88%

Influence of Labor on Neonatal Neutrophil Apoptosis, and Inflammatory Activity

et al. 2007

View full text Add to dashboard Cite

“…Differences in developmental stages, however, influence rate of spontaneous PMN apoptosis. PMN isolated from human umbilical cord blood exhibit decreased spontaneous apoptosis and impaired sensitivity to apoptosis-inducing agents, such as anti-Fas IgM and cycloheximide, compared with PMN derived from adults [6]. In cows, PMN apoptosis is influenced by stage of lactation.…”

Section: Regulation Of Pmn Life Spanmentioning

confidence: 99%

The bovine neutrophil: Structure and function in blood and milk

Paape¹,

Bannerman²,

et al. 2003

View full text Add to dashboard Cite

-Migration of polymorphonuclear neutrophil leukocytes (PMN) into the mammary gland provide the first line of defense against invading mastitis pathogens. Bacteria release potent toxins that activate white blood cells and epithelial cells in the mammary gland to secrete cytokines that recruit PMN that function as phagocytes at the site of infection. While freshly migrated PMN are active phagocytes, continued exposure of PMN to inhibitory factors in milk such as fat globules and casein, leads to altered PMN morphology and reduced phagocytosis. In the course of phagocytosing and destroying invading pathogens, PMN release chemicals that not only kill the pathogens but that also cause injury to the delicate lining of the mammary gland. This will result in permanent scarring and reduced numbers of milk secretory cells. The life span of PMN is limited by the onset of apoptosis. To minimize damage to mammary tissue, PMN undergo a specialized process of programmed cell death known as apoptosis. Macrophages quickly engulf and phagocytose apoptotic PMN, thereby minimizing the release of PMN granular contents that are damaging to tissue. The PMN possess an array of cell surface receptors that allow them to adhere and migrate through endothelium and to recognize and phagocytose bacteria. One receptor found on phagocytes that is receiving considerable attention in the control of infections by Gram-negative bacteria is CD14. Binding of lipopolysaccharide (LPS) to membrane bound CD14 causes release of tumor necrosis factor-a and sepsis. Binding of LPS to soluble CD14 shed from CD14-bearing cells results in neutralization of LPS and rapid recruitment of PMN to the site of infection. Recent advances in the fields of genomics and proteomics should greatly enhance our understanding of the PMN role in controlling intramammary infections in ruminants. Further, manipulation of PMN, through either recombinant proteins such as soluble CD14 that enhance PMN response or agents that mediate PMN apoptosis, may serve as novel therapeutics for the treatment of mastitis.

show abstract

Spontaneous and Fas-mediated apoptosis are diminished in umbilical cord blood neutrophils compared with adult neutrophils

Cited by 49 publications

References 53 publications

Neonatal Neutrophils with Prolonged Survival Exhibit Enhanced Inflammatory and Cytotoxic Responsiveness

Neonatal Neutrophils with Prolonged Survival Exhibit Enhanced Inflammatory and Cytotoxic Responsiveness

Influence of Labor on Neonatal Neutrophil Apoptosis, and Inflammatory Activity

The bovine neutrophil: Structure and function in blood and milk

Contact Info

Product

Resources

About