BACKGROUND: Recent years have seen increased levels of production and consumption of seafood, leading to more frequent reporting of allergic reactions in occupational and domestic settings. This review focuses on occupational allergy in the fishing and seafood processing industry. REVIEW: Workers involved in either manual or automated processing of crabs, prawns, mussels, fish, and fishmeal production are commonly exposed to various constituents of seafood. Aerosolisation of seafood and cooking fluid during processing are potential occupational situations that could result in sensitisation through inhalation. There is great variability of aerosol exposure within and among various jobs with reported allergen concentrations ranging from 0.001 to 5.061(microg/m(3)). Occupational dermal exposure occurs as a result of unprotected handling of seafood and its byproducts. Occupational allergies have been reported in workers exposed to arthropods (crustaceans), molluscs, pisces (bony fish) and other agents derived from seafood. The prevalence of occupational asthma ranges from 7% to 36%, and for occupational protein contact dermatitis, from 3% to 11%. These health outcomes are mainly due to high molecular weight proteins in seafood causing an IgE mediated response. Cross reactivity between various species within a major seafood grouping also occurs. Limited evidence from dose-response relations indicate that development of symptoms is related to duration or intensity of exposure. The evidence for atopy as a risk factor for occupational sensitisation and asthma is supportive, whereas evidence for cigarette smoking is limited. Disruption of the intact skin barrier seems to be an important added risk factor for occupational protein contact dermatitis. CONCLUSION: The range of allergic disease associated with occupational exposure to crab is well characterised, whereas for other seafood agents the evidence is somewhat limited. There is a need for further epidemiological studies to better characterise this risk. More detailed characterisation of specific protein antigens in aerosols and associated establishment of dose-response relations for acute and chronic exposure to seafood; the respective roles of skin contact and inhalational exposure in allergic sensitisation and cross reactivity; and the contribution of host associated factors in the development of occupational seafood allergies are important areas for future research. (+info)
Ron-mediated cytoplasmic signaling is dispensable for viability but is required to limit inflammatory responses.
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Ron receptor activation induces numerous cellular responses in vitro, including proliferation, dissociation, and migration. Ron is thought to be involved in blood cell development in vivo, as well as in many aspects of the immune response including macrophage activation, antigen presentation, and nitric oxide regulation. In previous studies to determine the function of Ron in vivo, mice were generated with a targeted deletion of the extracellular and transmembrane regions of this gene. Mice homologous for this deletion appear to die early during embryonic development. To ascertain the in vivo function of Ron in more detail, we have generated mice with a germline ablation of the tyrosine kinase domain. Strikingly, our studies indicate that this domain of Ron, and therefore Ron cytoplasmic signaling, is not essential for embryonic development. While mice deficient in this domain are overtly normal, mice lacking Ron signaling have an altered ability to regulate nitric oxide levels and, in addition, have enhanced tissue damage following acute and cell-mediated inflammatory responses. (+info)
Health effects of occupational exposure to acrylamide using hemoglobin adducts as biomarkers of internal dose.
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OBJECTIVES: This study assessed the health effects of occupational acrylamide exposure using hemoglobin (Hb) adducts as biomarkers of internal dose. METHODS: Two hundred and ten tunnel workers exposed for about 2 months to a chemical-grouting agent containing acrylamide and N-methylolacrylamide underwent a health examination. Blood samples were drawn for the analysis of Hb adducts of acrylamide. Fifty workers claiming recently developed or deteriorated symptoms of the peripheral nervous system (PNS) were referred to a neurophysiological examination. Workers with Hb-adduct levels exceeding 0.3 nmol/g globin attended follow-up examinations 6, 12, and 18 months after exposure cessation. RESULTS: Forty-seven workers had Hb-adduct levels within the normal background range (0.02-0.07 nmol/g globin), while the remaining 163 had increased levels up to a maximum of 17.7 nmol/g globin. Clear-cut dose-response associations were found between the Hb-adduct levels and PNS symptoms. Thirty-nine percent of those with Hb-adduct levels exceeding 1 nmol/g globin experienced tingling or numbness in their hands or feet. A no-observed adverse effect level of 0.51 nmol/g globin was estimated for numbness or tingling in the feet or legs. For 23 workers there was strong evidence of PNS impairment due to occupational exposure to acrylamide. All but two had recovered 18 months after the cessation of exposure. CONCLUSIONS: Occupational exposure to a grouting agent containing acrylamide resulted in PNS symptoms and signs. The use of Hb adducts of acrylamide as a biomarker of internal dose revealed strong dose-response associations. The PNS symptoms were, however, generally mild, and in almost all cases they were reversible. (+info)
Topical tacrolimus and cyclosporin A differentially inhibit early and late effector phases of cutaneous delayed-type and immunoglobulin E hypersensitivity.
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Systemic and topical administration routes of tacrolimus and cyclosporin A (CsA) were compared in effects on early and late phases of elicited T-cell-mediated contact sensitivity (CS), and effects on early and late phases of cutaneous immunoglobulin E (IgE) antibody-mediated hypersensitivity responses in mice. Thus, both CS and IgE responses in the skin have an early mast-cell-dependent phase, and also a late inflammatory phase. We measured the effects of both immunosuppressants on both phases of the respective T cell versus IgE responses. Systemic administration of both agents completely suppressed CS and IgE late-phase responses, but failed to affect either early phase. In contrast, when topical CsA was used, low doses abolished the early phase of IgE responses, but even high doses did not inhibit the early phase of CS. Conversely, topical tacrolimus inhibited the early phase of CS more potently than the early phase of cutaneous IgE hypersensitivity responses. Thus, topical treatment was needed to inhibit the early phases and the two agents acted differentially, suggesting differing susceptibility of the early phases, that are probably due to different signalling mechanisms. These studies underscore the potential value of topical administration of these powerful immunosuppressive agents in the treatment of allergic diseases that exhibit features of early-phase mast-cell-dependent inflammation, and late inflammation due to mast cells or to T cells, such as atopic dermatitis or asthma, since the early phase is predominantly susceptible to topical application, while the last phase of both IgE and T-cell inflammation responds to systemic treatment with both agents. (+info)
Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes.
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Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and alphav integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs. (+info)
Preferential usage of TCR-Vbeta17 by peripheral and cutaneous T cells in nickel-induced contact dermatitis.
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Nickel (Ni) is one of the most common contact sensitizers in man, and Ni-induced contact dermatitis is considered as a model of hapten-induced delayed type hypersensitivity. Previous studies indicated that Ni-reactive T cells derived from Ni-allergic individuals preferentially express distinct TCR-Vbeta chains. However, data on the TCR-Vbeta repertoire of Ni-responsive T cells are not consistent. Therefore, the aim of this study was to identify the TCR-Vbeta receptors of Ni-responsive peripheral and cutaneous T cells in a cohort of 17 donors with Ni-induced contact dermatitis in comparison with those of 6 healthy controls. Peripheral NiSO(4)-responsive T lymphocytes showed a significant overexpression of TCR-Vbeta17 and the frequency of TCR-Vbeta17(+) T cells correlated significantly with the in vitro reactivity of PBMC to NiSO(4). In addition, the cutaneous infiltrate of Ni-induced patch test reactions consisted primarily of Vbeta17(+) T cells. The majority of patch test-derived NiSO(4)-responsive T cells of three allergic donors were TCR-Vbeta17(+), whereas patch test-derived NiSO(4) unresponsive T cells of four additional donors did not express TCR-Vbeta17. Skin-derived Ni-responsive T cell lines from three donors uniformly secreted the Th2 cytokine, IL-5, but no IFN-gamma or IL-10. These in vitro and in vivo findings strongly suggest that T cells with a restricted TCR-Vbeta repertoire, i.e., Vbeta17, predominate in NiSO(4)-induced contact dermatitis and may be crucial in the effector phase of Ni hypersensitivity. (+info)
Tolerance to nickel: oral nickel administration induces a high frequency of anergic T cells with persistent suppressor activity.
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We adapted our mouse model of allergic contact hypersensitivity to nickel for the study of tolerance. Sensitization in this model is achieved by the administration of nickel ions with H(2)O(2); nickel ions alone are unable to prime naive T cells, but can restimulate primed ones. A 4-wk course of oral or i.p. administration of 10 mM NiCl(2) to naive mice induced tolerance, preventing the induction of hypersensitivity for at least 20 wk; long term desensitization of nickel-sensitized mice, however, required continuous NiCl(2) administration. When splenic T cells of orally tolerized donors, even after a treatment-free interval of 20 wk, were transferred to naive recipients, as with lymph node cells (LNC), they specifically prevented sensitization of the recipients. The LNC of such donors were anergic, because upon in vivo sensitization with NiCl(2) in H(2)O(2) and in vitro restimulation with NiCl(2), they failed to show the enhanced proliferation and IL-2 production as seen with LNC of mice not tolerized before sensitization. As few as 10(2) bulk T cells, consisting of both CD4(+) and CD8(+) cells, were able to specifically transfer tolerance to nickel. A hypothesis is provided to account for this extraordinarily high frequency of nickel-reactive, suppressive T cells; it takes into account that nickel ions fail to act as classical haptens, but form versatile, unstable metal-protein and metal-peptide complexes. Furthermore, a powerful amplification mechanism, such as infectious tolerance, must operate which allows but a few donor T cells to tolerize the recipient. (+info)
Increased and prolonged inflammation and angiogenesis in delayed-type hypersensitivity reactions elicited in the skin of thrombospondin-2--deficient mice.
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Angiogenesis and enhanced microvascular permeability are hallmarks of a large number of inflammatory diseases. Although up-regulation of proangiogenic factors such as vascular endothelial growth factor and interleukin-8 have been previously reported in inflamed tissue, the biologic role of endogenous inhibitors of angiogenesis in inflammation has remained unclear. To investigate the biologic role of the potent angiogenesis inhibitor thrombospondin-2 (TSP-2) in the control of cutaneous inflammation, delayed-type hypersensitivity reactions were elicited in the ear skin of wild-type and TSP-2-deficient mice by topical sensitization and challenge with oxazolone. Cutaneous TSP-2 expression was up-regulated in the inflamed skin of wild-type mice, predominantly in dermal fibroblasts and microvessels. Lack of TSP-2 resulted in a significantly enhanced inflammatory response with increased angiogenesis, edema formation, and inflammatory infiltration. Ear swelling and inflammation persisted for more than 2 weeks in TSP-2-deficient mice, as compared with 1 week in wild-type mice. Although baseline vascular permeability was unchanged, significantly enhanced microvascular leakage was found in the inflamed skin of TSP-2-deficient mice. Moreover, the fraction of rolling leukocytes was significantly increased in the untreated skin of TSP-2-deficient mice. These results reveal an important role of TSP-2 in limiting the extent and the duration of edema formation, angiogenesis, and inflammatory cell infiltration during acute and chronic inflammation. (+info)