Platelet factor 4 binds to interleukin 8 receptors and activates neutrophils when its N terminus is modified with Glu-Leu-Arg.

Clark‐Lewis, Ian; Dewald, Béatrice; Geiser, Thomas; Moser, Bernhard; Baggiolini, Marco

doi:10.1073/pnas.90.8.3574

Cited by 242 publications

(115 citation statements)

References 40 publications

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“…Chemokine PF4, which carries DLS (or DLQ) in these positions, fails to attract neutrophils. Addition of ELR residues to an N-terminally truncated PF4 increases its chemotactic potential for neutrophils (14). In vIL-8, DKR, a putative hybrid motif of ELR and DLS, is present in this region.…”

Section: Discussionmentioning

confidence: 99%

Marek's Disease Virus (MDV) Encodes an Interleukin-8 Homolog (vIL-8): Characterization of the vIL-8 Protein and a vIL-8 Deletion Mutant MDV

Parcells

Lin

Dienglewicz

et al. 2001

J Virol

154

134

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Chemokines induce chemotaxis, cell migration, and inflammatory responses. We report the identification of an interleukin-8 (IL-8) homolog, termed vIL-8, encoded within the genome of Marek's disease virus (MDV).The 134-amino-acid vIL-8 shares closest homology to mammalian and avian IL-8, molecules representing the prototype CXC chemokine. The gene for vIL-8 consists of three exons which map to the BamHI-L fragment within the repeats flanking the unique long region of the MDV genome. A 0.7-kb transcript encoding vIL-8 was detected in an n-butyrate-treated, MDV-transformed T-lymphoblastoid cell line, MSB-1. This induction is essentially abolished by cycloheximide and herpesvirus DNA polymerase inhibitor phosphonoacetate, indicating that vIL-8 is expressed with true late (␥ 2 ) kinetics. Baculovirus-expressed vIL-8 was found to be secreted into the medium and shown to be functional as a chemoattractant for chicken peripheral blood mononuclear cells but not for heterophils. To characterize the function of vIL-8 with respect to MDV infection in vivo, a recombinant MDV was constructed with a deletion of all three exons and a soluble-modified green fluorescent protein (smGFP) expression cassette inserted at the site of deletion. In two in vivo experiments, the vIL-8 deletion mutant (RB1BvIL-8⌬smGFP) showed a decreased level of lytic infection in comparison to its parent virus, an equal-passage-level parent virus, and to another recombinant MDV containing the insertion of a GFP expression cassette at the nonessential US2 gene. RB1BvIL-8⌬smGFP retained oncogenicity, albeit at a greatly reduced level. Nonetheless, we have been able to establish a lymphoblastoid cell line from an RB1BvIL-8⌬smGFP-induced ovarian lymphoma (MDCC-UA20) and verify the presence of a latent MDV genome lacking vIL-8. Taken together, these data describe the identification and characterization of a chemokine homolog encoded within the MDV genome that is dispensable for transformation but may affect the level of MDV in vivo lytic infection.

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Section: Discussionmentioning

confidence: 99%

Marek's Disease Virus (MDV) Encodes an Interleukin-8 Homolog (vIL-8): Characterization of the vIL-8 Protein and a vIL-8 Deletion Mutant MDV

Parcells

Lin

Dienglewicz

et al. 2001

J Virol

154

134

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“…The ELR ϩ CXC chemokines mediate their proangiogenic effects through a common receptor, CXCR2, which is predominantly found on vascular endothelial cells and neutrophils (16,17). Furthermore, we recently found that loss of CXCR2 inhibited tumor growth and angiogenesis in a murine model of lung cancer (18).…”

Section: R Enal Cell Carcinoma (Rcc)mentioning

confidence: 99%

The Role of CXCR2/CXCR2 Ligand Biological Axis in Renal Cell Carcinoma

Mestas¹,

Burdick²,

Reckamp³

et al. 2005

The Journal of Immunology

127

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Renal cell carcinoma (RCC) accounts for 3% of new cancer incidence and mortality in the United States. Studies in RCC have predominantly focused on VEGF in promoting tumor-associated angiogenesis. However, other angiogenic factors may contribute to the overall angiogenic milieu of RCC. We hypothesized that the CXCR2/CXCR2 ligand biological axis represents a mechanism by which RCC cells promote angiogenesis and facilitate tumor growth and metastasis. Therefore, we first examined tumor biopsies and plasma of patients with metastatic RCC for levels of CXCR2 ligands, and RCC tumor biopsies for the expression of CXCR2. The proangiogenic CXCR2 ligands CXCL1, CXCL3, CXCL5, and CXCL8, as well as VEGF were elevated in the plasma of these patients and found to be expressed within the tumors. CXCR2 was found to be expressed on endothelial cells within the tumors. To assess the role of ELR+ CXC chemokines in RCC, we next used a model of syngeneic RCC (i.e., RENCA) in BALB/c mice. CXCR2 ligand and VEGF expression temporally increased in direct correlation with RENCA growth in CXCR2+/+ mice. However, there was a marked reduction of RENCA tumor growth in CXCR2−/− mice, which correlated with decreased angiogenesis and increased tumor necrosis. Furthermore, in the absence of CXCR2, orthotopic RENCA tumors demonstrated a reduced potential to metastasize to the lungs of CXCR2−/− mice. These data support the notion that CXCR2/CXCR2 ligand biology is an important component of RCC tumor-associated angiogenesis and tumorigenesis.

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“…In CXC chemokines, an ELR motif occurs in several members of the class, such as IL-8, Gro-␣, -␤, and -␥, and NAP-2, and confers proangiogenic activity to the cytokines (4,5,18,19). For example, IL-8 induces in vitro endothelial cell chemotaxis and in vivo corneal neovascularization (8).…”

Section: Huvec Chemotaxis In Response Tomentioning

confidence: 99%

“…All CXC chemokines, such as IL-8, that function as PMN chemoattractants have a conserved Glu-Leu-Arg (ELR) motif near the N terminus. The ELR motif is critical for PMN receptor binding and PMN activation (4,5). Human mini TyrRS also has an ELR motif that is conserved among mammalian TyrRSs (3).…”

mentioning

confidence: 99%

Induction of Angiogenesis by a Fragment of Human Tyrosyl-tRNA Synthetase

Wakasugi

Slike

Hood

et al. 2002

Journal of Biological Chemistry

117

114

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The first step of protein synthesis is catalyzed by aminoacyl-tRNA synthetases. In addition, certain mammalian tRNA synthetases link protein synthesis to cytokine signaling pathways. In particular, human tyrosyl-tRNA synthetase (TyrRS) can be split by proteolysis into two fragments having distinct cytokine activities. One of the TyrRS fragments (mini TyrRS) contains features identical to those in CXC chemokines (like interleukin-8) that also act as angiogenic factors. Here mini TyrRS (but not full-length TyrRS) is shown to stimulate chemotaxis of endothelial cells in vitro and stimulate angiogenesis in each of two in vivo animal models. The angiogenic activity of mini TyrRS can be opposed by anti-angiogenic chemokines like IP-10. Thus, a biological fragment of human tyrosyl-tRNA synthetase links protein synthesis to regulation of angiogenesis.Previous work on human tyrosyl-tRNA synthetase (TyrRS)

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Platelet factor 4 binds to interleukin 8 receptors and activates neutrophils when its N terminus is modified with Glu-Leu-Arg.

Abstract: Amino

Cited by 242 publications

References 40 publications

Marek's Disease Virus (MDV) Encodes an Interleukin-8 Homolog (vIL-8): Characterization of the vIL-8 Protein and a vIL-8 Deletion Mutant MDV

Marek's Disease Virus (MDV) Encodes an Interleukin-8 Homolog (vIL-8): Characterization of the vIL-8 Protein and a vIL-8 Deletion Mutant MDV

The Role of CXCR2/CXCR2 Ligand Biological Axis in Renal Cell Carcinoma

Induction of Angiogenesis by a Fragment of Human Tyrosyl-tRNA Synthetase

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