A View to a Kill: Cytotoxic Mechanisms of Human Polymorphonuclear Leukocytes Compared with Monocytes and Natural Killer Cells

Kessel, van; Verhoef, J.

doi:10.1159/000163595

Cited by 22 publications

(8 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lysis of microorganisms by neutrophils has been studied extensively (54). A "bystander" killing of host cells by neutrophils as well as the killing of Ab-coated tumor cells has been described (55,56). Two of the essential effector molecules of neutrophils for the control of microbial infection are inducible NO and different reactive oxygen intermediates (57,58).…”

Section: Discussionmentioning

confidence: 99%

CD95 Ligand-Expressing Tumors Are Rejected in Anti-Tumor TCR Transgenic Perforin Knockout Mice

Behrens

Igney

Arnold

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

CD95 (APO-/Fas) ligand (CD95L) is a member of the TNF family predominantly expressed by activated T and NK cells but also by tumors of diverse cellular origin. CD95L trimerizes surface CD95 expressed by target cells that subsequently undergo apoptosis. The role of the CD95/CD95L system in the down-regulation of an immune response (activation-induced cell death) is established. However, it is so far unclear why tumors express CD95L. To investigate whether tumors use the CD95L to down-regulate an anti-tumor immune response, we established a transgenic (tg) mouse model consisting of 1) apoptosis-resistant tumor cells, designated LKC-CD95L, which express functional CD95L and the model tumor Ag Kb; and 2) perforin knockout (PKO) anti-Kb TCR tg mice. L1210-Fas antisense expressing Kb, crmA, and CD95L (LKC-CD95L) killed CD95+ unrelated tumor targets and Con A-activated splenocytes from anti-Kb TCR tg PKO mice by a CD95L-dependent mechanism in vitro. However, we could not detect any cytotoxic activity against anti-tumor (anti-Kb) T cells in vivo. We also observed reduced growth of LKC-CD95L in nude mice and rapid rejection in anti-Kb TCR tg PKO mice. Because the tumor cells are resistant to CD95L-, TNF-α-, and TNF-related apoptosis-inducing ligand-induced apoptosis and the mice used are perforin-deficient, the involvement of these four cytotoxicity mechanisms in tumor rejection can be excluded. The histological examination of tumors grown in nude mice showed infiltration of LKC-CD95L tumors by neutrophils, whereas L1210-Fas antisense expressing Kb and crmA (LKC) tumor tissue was neutrophil-free. Chemotaxis experiments revealed that CD95L has no direct neutrophil-attractive activity. Therefore, we conclude that LKC-CD95L cells used an indirect mechanism to attract neutrophils that may cause tumor rejection.

show abstract

Section: Discussionmentioning

confidence: 99%

CD95 Ligand-Expressing Tumors Are Rejected in Anti-Tumor TCR Transgenic Perforin Knockout Mice

Behrens

Igney

Arnold

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…With regard to the theoretically possible antitumour effector cells, the role of the induced IL-2 might be the activation of cytotoxic T cells or induction of lymphokine-activated killer cells [21,46]. Other mechanisms, like macrophage-or granulocyte-mediated cytotoxicity to tumour cells, may also be part of the mode of action of BCG [24,42]. Augmentation of these possible effector mechanisms by IL-l, IL-6, and TNFcz has been reported [10,23,34].…”

Section: Discussionmentioning

confidence: 99%

Induction of urinary interleukin-1 (IL-1), IL-2, IL-6, and tumour necrosis factor during intravesical immunotherapy with bacillus Calmette-Guérin in superficial bladder cancer

Boer

Jong

Steerenberg

et al. 1992

Cancer Immunol Immunother

178

View full text Add to dashboard Cite

To study the local immunological effects of intravesical bacillus Calmette-Guérin (BCG) therapy in superficial bladder cancer patients, the production of interleukin-1 (IL-1), IL-2, IL-6, tumour necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma) was investigated in the urine. Urine specimens were collected during the six weekly BCG instillations, before instillation, and 2, 4, 6, 8, and 24 h thereafter. Results were standardized to urine creatinine. In general, the concentration of IL-1 increased markedly during the first three BCG instillations, reaching a plateau from instillations 3 to 6. IL-2 was not detected after the first BCG instillation, but from the second instillation onwards the mean IL-2 concentration increased rapidly. With respect to IL-6, patients had relatively high levels in the urine after the first BCG instillation. A relatively moderate increase of the IL-6 concentration was observed during the following weeks. Like IL-2, TNF alpha was only detected after repeated BCG instillations. Generally the highest TNF levels were found after BCG instillation 5. The presence of IFN gamma could not be demonstrated. With respect to the occurrence of the cytokines during the first 24 h after the BCG instillation, TNF, IL-2, and IL-6 were detectable 2 h after the instillation. In contrast, IL-1 seemed to appear later, i.e. from 4 h onwards. TNF decreased most rapidly; it was nearly absent in 6-h samples. Generally IL-2 was not detectable in the 8-h samples, whereas IL-1 and IL-6 were present up to 8 h after instillation of BCG. The presence of TNF was found less frequently than the presence of IL-1, IL-2, and IL-6. Neutralization experiments indicated that most of the IL-1 present in the urine after BCG treatment was IL-1 alpha. In conclusion, activation of BCG-specific T cells was indicated by the detection of IL-2. The presence of IL-1, IL-6, and TNF alpha might suggest activation of macrophages by intravesically administered BCG, although production by other cell types cannot be excluded. It is suggested that these cytokines, in combination with the leucocytes that are known to be recruited to the bladder in reaction to the BCG treatment, may play an important role in the antitumour activity of BCG against bladder cancer. For monitoring purposes, collection of urine might be performed during the first 6 h after BCG instillations 4-6.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

“…They included cytotoxic macrophages, natural killer cells, specific cytotoxic T lymphocytes, and antibody-dependent cell cytotoxic effectors (8). Conversely, the antitumor effect of the neutrophils, which depend on classical cytotoxic systems, also has been suggested, including antibody-dependent cell cytotoxic effectors (9, 10), Fas ligand-mediated apoptosis (11), directed cell killing by H 2 O 2 and superoxide (12), and calprotectin (13).…”

Section: Introductionmentioning

confidence: 99%

Neutrophil-Derived TNF-Related Apoptosis-Inducing Ligand (TRAIL)

Koga¹,

Matsuzaki

Suminoe³

et al. 2004

Cancer Research

145

109

View full text Add to dashboard Cite

To detect the novel genes expressed uniquely in neutrophils and elucidate their function, the gene expression pattern was compared by using cDNA microarray containing 240 cytokine genes between the neutrophils and peripheral blood mononuclear cells (PBMCs) obtained from healthy human donors. Twenty-six genes, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were expressed in neutrophils at a level >10 times higher than that seen in phytohemagglutinin-stimulated PBMCs. The amounts of mRNA and protein of TRAIL were quantified by real-time reverse transcription-PCR and ELISA, respectively. TRAIL was expressed in resting neutrophils at the mRNA and protein levels, and its expression was enhanced after stimulation with IFN-␥. Neutrophils expressed TRAIL on the cell surface and released it into the culture media. The cytotoxicity of neutrophil-derived TRAIL against Jurkat cells was determined by flow cytometry using FITC-conjugated annexin V. When Jurkat cells were cultured with neutrophils in the presence of IFN-␥, the number of Jurkat cells undergoing apoptosis increased, and such increase depended on the effector:target ratio. This cytotoxicity was suppressed partially by adding anti-TRAIL antibody to the media. Neutrophils may exert their own antitumor effect by TRAIL. A microarray analysis was found to be a useful tool for detecting novel genes that are suggested to play unknown roles in the neutrophil function.

show abstract

A View to a Kill: Cytotoxic Mechanisms of Human Polymorphonuclear Leukocytes Compared with Monocytes and Natural Killer Cells

Cited by 22 publications

References 48 publications

CD95 Ligand-Expressing Tumors Are Rejected in Anti-Tumor TCR Transgenic Perforin Knockout Mice

CD95 Ligand-Expressing Tumors Are Rejected in Anti-Tumor TCR Transgenic Perforin Knockout Mice

Induction of urinary interleukin-1 (IL-1), IL-2, IL-6, and tumour necrosis factor during intravesical immunotherapy with bacillus Calmette-Guérin in superficial bladder cancer

Neutrophil-Derived TNF-Related Apoptosis-Inducing Ligand (TRAIL)

Contact Info

Product

Resources

About