Recombinant tumor necrosis factor causes activation of human granulocytes

Larrick, J W; Graham, D; Toy, K; Lin, LS; Senyk, G; Fendly, BM

doi:10.1182/blood.v69.2.640.bloodjournal692640

Cited by 3 publications

(1 citation statement)

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“…TNF is recognized as a central initiator in the inflammatory process, which includes the priming and activation of PMNs (52)(53)(54). TNF primes PMNs for an enhanced response to subsequent insults (55), up-regulates adhesion molecules causing PMNs adherence to the vascular endothelium (53), and en-hances neutrophil superoxide production (54). Preventing serum TNF levels from reaching pathologic concentrations is an attractive strategy for reducing the incidence of ARDS.…”

Section: Blockade Of Initiator: Tnfmentioning

confidence: 99%

Systemic Inflammation Induced by Cardiopulmonary Bypass: A Review of Pathogenesis and Treatment

Nieman

Searles²,

Carney

et al. 1999

J Extra Corpor Technol

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The acute respiratory distress syndrome (ARDS) is a severe alteration in lung structure and function that develops secondary to a traumatic stimulus. When ARDS develops following cardiopulmonary bypass (CPB) it is know as postpump syndrome (PPS). ARDS can be caused by a single massive insult (“hit”); however, sequential minor insults (“hits”) are more common clinically. The concept of multiple sequential insults causing ARDS has been termed the “two-hit” model of ARDS. The purpose of this article is to summarize our studies testing the hypothesis that PPS is caused by multiple sequential insults. To confirm our hypothesis, we developed a porcine model of “two-hit” PPS. Our model was composed of sequential benign insults, with CPB as the “first hit” and low dose of endotoxin as the “second-hit.” It is our hypothesis that the mechanism of PPS is CPB-induced priming of polymorphonuclear leukocytes (PMNs) (“first-hit”) with subsequent PMN activation by a second insult (“second-hit”) such as endotoxin. Our model confirms this clinically relevant postulate, and we provide strategies to disrupt the inflammatory cascade leading to PPS.

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Section: Blockade Of Initiator: Tnfmentioning

confidence: 99%

Systemic Inflammation Induced by Cardiopulmonary Bypass: A Review of Pathogenesis and Treatment

Nieman

Searles²,

Carney

et al. 1999

J Extra Corpor Technol

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Increased TNF-α-Induced Apoptosis in Lymphocytes from Aged Humans: Changes in TNF-α Receptor Expression and Activation of Caspases

Aggarwal

Gollapudi

Gupta

1999

The Journal of Immunology

184

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Aging is characterized by increased T cell lymphopenia, T cell dysfunction, and increased serum TNF levels. In this study, we have examined the role of TNF-induced apoptosis in T cell deficiency in lymphocytes from aged humans. The constitutive expression of TNF receptors (TNFRI and TNFRII) and the adapter molecules, including TNFR-associated death domain protein (TRADD), TNFR-associated factor 2 (TRAF-2), and receptor interacting protein (RIP), were analyzed both at the protein level by flow cytometry or Western blotting, and at the mRNA level using quantitative PCR or Northern blotting in lymphocytes from aged and young subjects. The susceptibility of T cells to undergo TNF-induced apoptosis was analyzed using terminal deoxynucleotidyltransferase-mediated UTP-end-labeling (TUNEL) and DNA ladder assays. Caspase (caspase-8 and caspase-3) activation was compared between aged and young subjects using Western blotting and colorimetric assays. In lymphocytes from aged humans, there was an increased susceptibility of CD4+ and CD8+ T cells to undergo TNF-α-induced apoptosis, as observed by TUNEL assay and DNA fragmentation ladder assay. Increased TNF-α-induced apoptosis was also observed in both CD45RA+ and CD45RO+ T cells from aging subjects. An increased constitutive expression of TNFRI and TRADD and decreased expression of TNFRII and TRAF-2 were observed in lymphocytes from aged as compared with young controls. In addition, there was an early and increased activation of caspases (caspase-8 and caspase-3) involved in TNFR/TNF signaling pathway, as evident by early cleavage of caspase-8, poly(ADP-ribose) polymerase (PARP), and caspase-3 substrate DEVD-p-nitroamilide NA. These data suggest that an increased TNF-α-induced apoptosis may play a role in T cell deficiency associated with human aging.

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Unique Effect of Arachidonic Acid on Human Neutrophil TNF Receptor Expression: Up-Regulation Involving Protein Kinase C, Extracellular Signal-Regulated Kinase, and Phospholipase A2

Moghaddami

Costabile

Grover

et al. 2003

The Journal of Immunology

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Arachidonic acid (AA) regulates the function of many cell types, including neutrophils. Although much emphasis has been placed on agonist-induced down-regulation of TNFR, our data show that AA caused a rapid (10–20 min) and dose-dependent (0.5–30 μM) increase in the surface expression of both classes of TNFR (TNFR1 and TNFR2) on human neutrophils. This increased TNFR expression correlated with an increase in TNF-induced superoxide production. In contrast, the ω3 fatty acids eicosapentaenoic acid, docosahexaenoic acid, and linolenic acid failed to stimulate TNFR expression. Although fMLP and LPS reduced the neutrophil expression of TNFR, when pretreated with AA, fMLP caused an increase in TNFR expression. Consistent with this result was the finding that AA prevented the fMLP-induced receptor release in neutrophil cultures. AA also caused an increase in TNFR expression in matured HL-60 cells (neutrophil-like cells), but a decrease in nonmatured cells and HUVEC. The AA effects were independent of the lipoxygenase and cyclooxygenase pathways, but dependent on protein kinase C, the extracellular signal-regulated kinases 1 and 2, and cytosolic phospholipase A2. The data demonstrate a unique effect of AA in the inflammatory reaction, through its action on neutrophil TNFR expression, and suggest that AA may regulate the response of neutrophils to TNF by altering its receptor number.

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Recombinant tumor necrosis factor causes activation of human granulocytes

Cited by 3 publications

References 0 publications

Systemic Inflammation Induced by Cardiopulmonary Bypass: A Review of Pathogenesis and Treatment

Systemic Inflammation Induced by Cardiopulmonary Bypass: A Review of Pathogenesis and Treatment

Increased TNF-α-Induced Apoptosis in Lymphocytes from Aged Humans: Changes in TNF-α Receptor Expression and Activation of Caspases

Unique Effect of Arachidonic Acid on Human Neutrophil TNF Receptor Expression: Up-Regulation Involving Protein Kinase C, Extracellular Signal-Regulated Kinase, and Phospholipase A2

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