Intralesional Cytokines in Chronic Oxazolone-Induced Contact Sensitivity Suggest Roles for Tumor Necrosis Factor α and Interleukin-4

Webb, Edward F.; Tzimas, Maritsa N.; Griswold, Don E.; Newsholme, Stephen J.

doi:10.1046/j.1523-1747.1998.00239.x

Cited by 61 publications

(86 citation statements)

References 20 publications

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“…2 These highlight the importance of lymph flow, which delivers antigen to the lymph node, to adaptive immunity. Whereas increased levels of cytokine production is observed from 4 hours, peaking at 16 hours after challenge in a skin lesion model, 39 increased interstitial flow is an immediate response to certain types of peripheral inflammation. 6 Our data show that both fluid and cell transport are enhanced on increased flow, and because flow can increase immediately, it is likely to be an important mediator of early responses to inflammation.…”

Section: Discussionmentioning

confidence: 93%

Transmural Flow Modulates Cell and Fluid Transport Functions of Lymphatic Endothelium

Miteva

Rutkowski

Dixon

et al. 2010

Circulation Research

224

191

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Key Words: CCL21 Ⅲ ICAM-1 Ⅲ inflammation Ⅲ lymphedema Ⅲ in vitro Ⅲ overhydration I mmune functions of lymphatic endothelium include the transport of interstitial fluid to the lymph node, which provides constant sampling of peripheral antigens to antigenpresenting cells such as dendritic cells (DCs), macrophages, and B cells residing in the lymphatic endothelium, 1,2 and cell transport from the periphery to the lymph node. 3 These processes are important both for inducing an adaptive immune response as well as for maintaining tolerance to self-antigens. 4 Despite its importance, the active regulation of fluid and cell transport by lymphatic endothelium is largely unexplored. We asked how the lymphatic endothelium might sense and respond to its local physical environment to regulate these functions, particularly with respect to inflammation and tissue injury.Arguably, the first events in tissue injury and inflammation include the rapid release of mediators that increase the permeability of the local blood vessels, which leads to influx of plasma fluid and proteins into the interstitium, elevated interstitial fluid pressure, and increased lymph flow. [5][6][7][8] This is followed by the release of inflammatory cytokines such as tumor necrosis factor (TNF)-␣. Recently, several inflammatory cues including TNF-␣, TNF-␤, and interleukin-1, as well as pathogenic signals such as bacterial lipopolysaccharide (LPS), were shown to influence immune cell traffic into lymphatics by modulating lymphatic endothelial expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule-1 (VCAM-1), and selectin (endothelial adhesion molecule 1 or CD62E), 9 -11 which are used by DCs for transmigration into lymphatics.Whereas the expression of such inflammatory cytokines following tissue injury can take several hours, 12 heightened lymph flow increases almost immediately. [5][6][7][8] We hypothesized that heightened transmural flow could act as an immediate cue for signaling injury or inflammatory conditions to lymphatic endothelium, driving changes in lymphatic endothelial transport functions to modulate fluid and DC trafficking to the draining lymph node. This could potentially act alone or in concert with inflammatory cytokines. Other recent evidence points to fluid shear stress as a modulator of nitric oxide release and lymphatic pump function in contractile lymphatics, 13,14 regulate leukocyte adhesion and transmigration events in blood endothelium. 15,16 However, the role of transmural flow on lymphatic endothelium and its transport functions has not been examined to date, and whereas leukocytes exiting blood vessels experience a high-shear environment before and during their transmigration, leukocytes entering lymphatics do not experience such conditions in the basal interstitium. Because lymphatic capillaries play a different role in inflammation than blood capillaries, their functional responses to environmental cues need to be separately investigated.Here, using both in vivo and in vitro systems, we d...

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Section: Discussionmentioning

confidence: 93%

Transmural Flow Modulates Cell and Fluid Transport Functions of Lymphatic Endothelium

Miteva

Rutkowski

Dixon

et al. 2010

Circulation Research

224

191

View full text Add to dashboard Cite

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“…While the reaction to oxazolone is predominantly a Th1-dependent response in which both TNF-a and IFN-c have been shown to play a role, multiple other cytokines such as IL-4, IL-10 and IL-6 have also been shown to participate in this response [26,[35][36][37][38]. Previous studies have suggested that TNF-a is the main inflammatory cytokine, as blockade of TNF-a prevented the CS response, while IFN-c blockade only had a partial protective effect [35,36].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that TNF-a is present in the skin very early after challenge, with peak levels seen 4 h post-hapten challenge [26]. IFN-c levels are also increased significantly by 4 h with peak levels observed at 12-16 h post-hapten challenge [26]. Given the different time profiles of cytokine expression, the early, intermediate and late phases of the CS response were examined.…”

Section: No Can Down-regulate Lymphocyte Recruitment During the Elicimentioning

confidence: 99%

Interferon‐γ limits Th1 lymphocyte adhesion to inflamed endothelium: A nitric oxide regulatory feedback mechanism

Norman¹,

Zbytnuik²,

Kubes³

2008

Eur J Immunol

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AustraliaCD4 + T helper (Th1 and Th2) cell localization to a site of inflammation is important for the development, maintenance and regulation of an immune response. The factors that regulate Th1 and Th2 cell recruitment into tissue are not fully understood. The aim of the present study was to examine the effect of different cytokine microenvironments on the recruitment of Th1 and Th2 lymphocytes into tissue. Fluorescently labelled Th1 or Th2 lymphocyte-endothelial interactions were observed via intravital microscopy of the cytokine-treated cremaster muscle. Our results show that TNF-a alone is sufficient to maximally recruit Th1 cells. Surprisingly, treatment with TNF-a + IFN-c significantly decreased Th1 adhesion and emigration in comparison to TNF-a treatment alone. The decreased adhesion of Th1 cells in response to TNF-a + IFN-c reflected a decreased ability to bind to ICAM-1 and was iNOS-dependent. This phenomenon was not observed with Th2 cells. These results suggest that IFN-c may play a key immunomodulatory role in the recruitment of different T lymphocyte subsets. Indeed, blockade of IFN-c or iNOS function during the Th1-mediated contact hypersensitivity response resulted in an acceleration and exacerbation of the late-phase inflammatory response.

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“…IgE-triggered release of mediators by dermal mast cells is responsible for onset of the edema response that occurs 30 min after elicitation (9,13). Therefore, serum total IgE levels were assessed on days 0, 7, 14, and 24 of Ag challenge.…”

Section: Adhesion Molecule Deficiency Suppressed Serum Ige Levelsmentioning

confidence: 99%

L-Selectin or ICAM-1 Deficiency Reduces an Immediate-Type Hypersensitivity Response by Preventing Mast Cell Recruitment in Repeated Elicitation of Contact Hypersensitivity

Shimada

Hasegawa

Kaburagi

et al. 2003

The Journal of Immunology

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Repeated Ag exposure results in a shift in the time course of contact hypersensitivity (CH) from a typical delayed-type to an immediate-type response followed by a late phase reaction. Chronic CH responses are clinically relevant to human skin allergic diseases, such as atopic dermatitis, that are usually caused by repeated stimulation with environmental Ags. Chronic inflammatory responses result in part from infiltrating leukocytes. To determine the role of leukocyte adhesion molecules in chronic inflammation, chronic CH responses were assessed in mice lacking L-selectin, ICAM-1, or both adhesion molecules. Following repeated hapten sensitization for 24 days at 2-day intervals, wild-type littermates developed an immediate-type response at 30 min after elicitation, followed by a late phase reaction. By contrast, loss of ICAM-1, L-selectin, or both, eliminated the immediate-type response and inhibited the late phase reaction. Similar results were obtained when wild-type littermates repeatedly exposed to hapten for 22 days were treated with mAbs to L-selectin and/or ICAM-1 before the elicitation on day 24. The lack of an immediate-type response on day 24 paralleled a lack of mast cell accumulation after 30 min of elicitation and decreased serum IgE production. Repeated Ag exposure in wild-type littermates resulted in increased levels of serum L-selectin, a finding also observed in atopic dermatitis patients. The current study demonstrates that L-selectin and ICAM-1 cooperatively regulate the induction of the immediate-type response by mediating mast cell accumulation into inflammatory sites and suggests that L-selectin and ICAM-1 are potential therapeutic targets for regulating human allergic reactions.

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Intralesional Cytokines in Chronic Oxazolone-Induced Contact Sensitivity Suggest Roles for Tumor Necrosis Factor α and Interleukin-4

Cited by 61 publications

References 20 publications

Transmural Flow Modulates Cell and Fluid Transport Functions of Lymphatic Endothelium

Transmural Flow Modulates Cell and Fluid Transport Functions of Lymphatic Endothelium

Interferon‐γ limits Th1 lymphocyte adhesion to inflamed endothelium: A nitric oxide regulatory feedback mechanism

L-Selectin or ICAM-1 Deficiency Reduces an Immediate-Type Hypersensitivity Response by Preventing Mast Cell Recruitment in Repeated Elicitation of Contact Hypersensitivity

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