Platelet-Activating Factor Is Crucial in Psoralen and Ultraviolet A-Induced Immune Suppression, Inflammation, and Apoptosis

Wolf, Peter; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Byrne, Scott N.; Matsumura, Yasuhiro; Matsumura, Yasuhiro; Bucana, C. D.; Ananthaswamy, Honnavara N.; Ullrich, Stephen E.

doi:10.2353/ajpath.2006.060079

Cited by 98 publications

(97 citation statements)

References 55 publications

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“…For example, Silva et al (38) showed that oxidized lipids, including PAF, induced the expression of a wide range of chemokines. Because of the critical role PAF plays in UV-induced immune suppression (14,15), it is tempting to speculate that PAF is driving UV-induced CXCL12 expression. Another possible CXCL12 trigger might be the multitude of cytokines released following UV exposure including IL-4, IL-10, and TNF (39).…”

Section: Discussionmentioning

confidence: 99%

“…This is perhaps not surprising when one considers the wide range of inflammatory mediators and cytokines that mast cells have been shown to produce (10). Indeed, many of the inflammatory mediators released by mast cells including, histamine (10,11), PGE 2 (12), serotonin (13), platelet-activating factor (PAF) (14,15) TNF, IL-4, and IL-10 (16) are critical mediators of UV-induced immunosuppression. Grimbaldeston et al (17) recently demonstrated that mast cell-derived IL-10 limits the skin pathology associated with contact dermatitis and chronic inflammation induced by UV exposure, again reinforcing the growing appreciation for the ability of mast cells to regulate inflammation and the immune response.…”

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confidence: 99%

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Mast Cell Migration from the Skin to the Draining Lymph Nodes upon Ultraviolet Irradiation Represents a Key Step in the Induction of Immune Suppression

Byrne

Limón-Flores

Ullrich³

2008

The Journal of Immunology

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144

170

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The UV radiation in sunlight is the primary cause of skin cancer. UV is also immunosuppressive and numerous studies have shown that UV-induced immune suppression is a major risk factor for skin cancer induction. Previous studies demonstrated that dermal mast cells play a critical role in the induction of immune suppression. Mast cell-deficient mice are resistant to the immunosuppressive effects of UV radiation, and UV-induced immune suppression can be restored by injecting bone marrow-derived mast cells into the skin of mast cell- deficient mice. The exact process however, by which mast cells contribute to immune suppression, is not known. In this study, we show that one of the first steps in the induction of immune suppression is mast cell migration from the skin to the draining lymph nodes. UV exposure, in a dose-dependent manner, causes a significant increase in lymph node mast cell numbers. When GFP+ skin was grafted onto mast cell-deficient mice, we found that GFP+ mast cells preferentially migrated into the lymph nodes draining the skin. The mast cells migrated primarily to the B cell areas of the draining nodes. Mast cells express CXCR4+ and UV exposure up-regulated the expression of its ligand CXCL12 by lymph node B cells. Treating UV-irradiated mice with a CXCR4 antagonist blocked mast cell migration and abrogated UV-induced immune suppression. Our findings indicate that UV-induced mast cell migration to draining lymph nodes, mediated by CXCR4 interacting with CXCL12, represents a key early step in UV-induced immune suppression.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Mast Cell Migration from the Skin to the Draining Lymph Nodes upon Ultraviolet Irradiation Represents a Key Step in the Induction of Immune Suppression

Byrne

Limón-Flores

Ullrich³

2008

The Journal of Immunology

Self Cite

144

170

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“…UVB is immunosuppressive and facilitates progression of non-melanoma skin cancer, and it has been proposed 24 that PAF and/or PAF-like lipids mediate this systemic immune suppression via PAF-receptor-mediated IL-10 production. Moreover, topical psoralen + UVA-mediated keratinocyte cytotoxicity has been reported to be decreased in PAF-receptor deficient mice in comparison to wild-type counterparts 28 .…”

Section: Paf System and Uvrmentioning

confidence: 99%

Oxidized glycerophosphocholines as biologically active mediators for ultraviolet radiation-mediated effects

Konger

Marathe

Yao

et al. 2008

Prostaglandins & Other Lipid Mediators

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Ultraviolet light radiation (UVR) has profound effects upon human skin. Yet, the exact targets for UVR are unclear. Inasmuch as UVR is a known pro-oxidative stressor, one potential target for UVR could be oxidatively modified glycerophosphocholines (GPC). Importantly, recent studies demonstrate that these oxidized GPCs (ox-GPC) are potent agonists for the platelet-activating factor receptor and peroxisome proliferator-activated receptor gamma. This review discusses these new biologically active lipids and their down-stream receptor targets that provide a unique system of biosensors for detecting and responding to UVR photo-oxidation.

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“…PAF is produced by physical stress, including UV light and trauma (14). PAF is involved in UVB, psoralen plus UVA light, and jet fuel-induced immune suppression (13,15,16). PAF also plays a role in regulating the immune response to microbial pathogens (14).…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Dermal Dendritic Cells, and Not Langerhans Cells, Play an Essential Role in Inducing an Immune Response

Fukunaga

Khaskhely

Sreevidya

et al. 2008

The Journal of Immunology

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Langerhans cells (LCs) serve as epidermal sentinels of the adaptive immune system. Conventional wisdom suggests that LCs encounter Ag in the skin and then migrate to the draining lymph nodes, where the Ag is presented to T cells, thus initiating an immune response. Platelet-activating factor (PAF) is a phospholipid mediator with potent biological effects. During inflammation, PAF mediates recruitment of leukocytes to inflammatory sites. We herein tested a hypothesis that PAF induces LC migration. Applying 2,4-dinitro-1-fluorobenzene (DNFB) to wild-type mice activated LC migration. In contrast, applying DNFB to PAF receptor-deficient mice or mice injected with PAF receptor antagonists failed to induce LC migration. Moreover, after FITC application the appearance of hapten-laden LCs (FITC+, CD11c+, Langerin+) in the lymph nodes of PAF receptor-deficient mice was significantly depressed compared with that found in wild-type mice. LC chimerism indicates that the PAF receptor on keratinocytes but not LCs is responsible for LC migration. Contrary to the diminution of LC migration in PAF receptor-deficient mice, we did not observe any difference in the migration of hapten-laden dermal dendritic cells (FITC+, CD11c+, Langerin−) into the lymph nodes of PAF receptor-deficient mice. Additionally, the contact hypersensitivity response generated in wild-type or PAF receptor-deficient mice was identical. Finally, dermal dendritic cells, but not LCs isolated from the draining lymph nodes after hapten application, activated T cell proliferation. These findings suggest that LC migration may not be responsible for the generation of contact hypersensitivity and that dermal dendritic cells may play a more important role.

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Platelet-Activating Factor Is Crucial in Psoralen and Ultraviolet A-Induced Immune Suppression, Inflammation, and Apoptosis

Cited by 98 publications

References 55 publications

Mast Cell Migration from the Skin to the Draining Lymph Nodes upon Ultraviolet Irradiation Represents a Key Step in the Induction of Immune Suppression

Mast Cell Migration from the Skin to the Draining Lymph Nodes upon Ultraviolet Irradiation Represents a Key Step in the Induction of Immune Suppression

Oxidized glycerophosphocholines as biologically active mediators for ultraviolet radiation-mediated effects

Dermal Dendritic Cells, and Not Langerhans Cells, Play an Essential Role in Inducing an Immune Response

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