The involvement of CD14 in stimulation of cytokine production by uronic acid polymers

Espevik, Terje; Otterlei, M.; Skjåk‐Bræk, Gudmund; Ryan, Liv; Wright, Samuel D.; Sundan, Anders

doi:10.1002/eji.1830230140

Cited by 194 publications

(115 citation statements)

References 32 publications

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“…Soluble alginate rich in mannuronic acid (>86%) is able to induce TNF in monocytes through mechanisms involving CD14 [30] TLR2 and TLR4 [31]. Recently it was demonstrated that purified alginate rich in guluronic acid as used currently, did not activate TLRs [32].…”

Section: Cd11b Cd18 or Cd11c Blockagementioning

confidence: 99%

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Ørning

Hoem

Coron

et al. 2016

Journal of Controlled Release

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The inflammatory potential of 12 types of alginate-based microspheres was assessed in a human whole blood model. The inflammatory potential could be categorized from low to high based on the four main alginate microsphere types; alginate microbeads, liquefied core poly-L-ornithine (PLO)-containing microcapsules, liquefied core poly-L-lysine (PLL)-containing microcapsules, and solid core PLLcontaining microcapsules. No complement or inflammatory cytokine activation was detected for the Ca/Ba alginate microbeads. Liquefied core PLO-and PLL-containing microcapsules induced significant fluid phase complement activation (TCC), but with low complement surface deposition (anti-C3c), and a low proinflammatory cytokine secretion, with exception of an elevated MCP-1(CCL2) secretion. The solid core PLL-containing microcapsules generated lower TCC but a marked complement surface deposition and significant induction of the proinflammatory cytokines interleukin (IL-1)β, TNF, IL-6, the chemokines IL-8 (CXCL8), and MIP-1α (CCL3) and MCP-1(CCL2).Inhibition with compstatin (C3 inhibitor) completely abolished complement surface deposition, leukocyte adhesion and the proinflammatory cytokines. The C5 inhibitions partly lead to a reduction of the proinflammatory cytokines. The leukocyte adhesion was abolished by inhibitory antibodies against CD18 and partly reduced by CD11b, but not by CD11c. Anti-CD18 significantly reduced the (IL-1)β, TNF, IL-6 and MIP-1α and anti-CD11b significantly reduced the IL-6 and VEGF secretion. MCP-1 was strongly activated by anti-CD18 and anti-CD11b. In conclusion the initial proinflammatory cytokine responses are driven by the microspheres potential to trigger complement C3 (C3b/iC3b) deposition, leukocyte activation and binding through complement receptor CR3 (CD11b/CD18).MCP-1 is one exception dependent on the fluid phase complement activation mediated through CR3.

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Section: Cd11b Cd18 or Cd11c Blockagementioning

confidence: 99%

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Ørning

Hoem

Coron

et al. 2016

Journal of Controlled Release

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“…The receptor for mannuronan on human monocytes is CD14 [8], which also is a functional receptor for LPS [10]. CD14 may exist as a soluble molecule (sCD14) and is thought to mediate LPS effects on cells that do not express the membrane form [27].…”

Section: Discussionmentioning

confidence: 99%

“…It also binds to membrane CD14 [8,9], and requires serum or lipopolysaccharide-binding protein (LBP) for TNF production [8,9]. The CD14 receptor also binds LPS and mediates LPS effects [10].…”

Section: Introductionmentioning

confidence: 99%

Mannuronan Enhances Survival of Lethally Irradiated Mice and Stimulates Murine Haematopoiesis In Vitro

et al. 1997

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Halaas Ø, Olsen WM, Veiby OP, Løvhaug D, Skjåk-Braek G, Vik R, Espevik T. Mannuronan Enhances Survival of Lethally Irradiated Mice and Stimulates Murine Haematopoiesis In Vitro. Scand J Immunol 1997;46:358-365 Mannuronan (poly-b-(1→4)-D-mannuronate or poly-M), produced by Pseudomonas aeruginosa as a mucoid exopolysaccharide, has previously been shown to exhibit immunostimulating activity. The authors investigated the in vivo and in vitro effects of mannuronan on murine haematopoiesis. In vivo, prophylactic (¹24 h, intraperitoneal) administration of mannuronan enhanced survival of lethally irradiated mice from zero day 40 survivors (NaCl) to 20, 80 and 70% survival at 0.5, 1 and 2 mg/kg bw mannuronan, respectively. In vitro, primary stromal cultures stimulated with mannuronan produced high levels of interleukin(IL)-1, IL-6 and colony stimulating activity. Mannuronan alone did not have any colony stimulating activity on GM-CFC, BFU-E, Mix-CFC or HPP-CFC progenitors in clonogenic assays, but acted synergistically with suboptimal amounts of growth factors on GM-CFC, Mix-CFC and HPP-CFC colony formation. Limiting dilution analysis showed that 1 of 423 bone marrow cells formed colonies in response to suboptimal GM-CSF plus mannuronan compared to 1 of 592 for suboptimal GM-CSF alone. The primitive Lin ¹ Sca-1 þ haematopoietic progenitors showed increased day 10 colony size in the presence of mannuronan in single cell assays. These stimulating effects of mannuronan on haematopoiesis may prove to have clinical importance.

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“…(Wright et al, 1990;Espevik et al, 1993;Haziot et al, 1996;Weidemann et al, 1997;Dziarski et al, 1998;Ingalls et al, 1999). CD14 also involves in TLR2-dependent initiation of immune response (Schroder et al, 2003), however, depending on the nature of the ligand, the presence of which is not absolutely required by all TLR2 complexes for signaling activity (Jiang et al, 2005).…”

Section: Tlr2mentioning

confidence: 99%

Herpesviral infection and Toll-like receptor 2

Cai

Zheng

2012

Protein Cell

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In the last decade, substantial progress has been made in understanding the molecular mechanisms involved in the initial host responses to viral infections. Herpesviral infections can provoke an inflammatory cytokine response, however, the innate pathogen-sensing mechanisms that transduce the signal for this response are poorly understood. In recent years, it has become increasingly evident that the Toll-like receptors (TLRs), which are germline-encoded pattern recognition receptors (PRRs), function as potent sensors for infection. TLRs can induce the activation of the innate immunity by recruiting specific intracellular adaptor proteins to initiate signaling pathways, which then culminating in activation of the nuclear factor kappa B (NF-κB) and interferon-regulatory factors (IRFs) that control the transcription of genes encoding type I interferon (IFN I) and other inflammatory cytokines. Furthermore, activation of innate immunity is critical for mounting adaptive immune responses. In parallel, common mechanisms used by viruses to counteract TLR-mediated responses or to actively subvert these pathways that block recognition and signaling through TLRs for their own benefit are emerging. Recent findings have demonstrated that TLR2 plays a crucial role in initiating the inflammatory process, and surprisingly that the response TLR2 triggers might be overzealous in its attempt to counter the attack by the virus. In this review, we summarize and discuss the recent advances about the specific role of TLR2 in triggering inflammatory responses in herpesvirus infection and the consequences of the alarms raised in the host that they are assigned to protect.

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The involvement of CD14 in stimulation of cytokine production by uronic acid polymers

Cited by 194 publications

References 32 publications

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Mannuronan Enhances Survival of Lethally Irradiated Mice and Stimulates Murine Haematopoiesis In Vitro

Herpesviral infection and Toll-like receptor 2

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