Lymphatic Dysfunction Impairs Antigen-Specific Immunization, but Augments Tissue Swelling Following Contact with Allergens

The lymph transports tissue-resident dendritic cells (DCs) to regional lymph nodes (LNs), having important roles in immune function. The biological effects on tissue inflammation following lymphatic flow obstruction in vivo, however, are not fully known. In this study, we investigated the role of the lymphatic system in contact hypersensitivity (CHS) responses using k-cyclin transgenic (kCYC+/-) mice, which demonstrate severe lymphatic dysfunction. kCYC+/- mice showed enhanced ear swelling to both DNFB and FITC, as well as stronger irritant responses to croton oil compared with wild-type littermates. Consistently, challenged ears of kCYC+/- mice exhibited massive infiltrates of inflammatory cells. In contrast, DC migration to regional LNs, drainage of cell-free antigen to LNs, antigen-specific IFN-γ production, and lymphocyte proliferation were impaired during the sensitization phase of CHS in kCYC+/- mice. Transfer experiments using lymphocytes from sensitized mice and real-time PCR analysis of cytokine expression using challenged ear revealed that ear swelling was enhanced because of impaired lymphatic flow. Collectively, we conclude that insufficient lymphatic drainage augments apparent inflammation to topically applied allergens and irritants. The findings add insight into the clinical problem of allergic and irritant contact dermatitis that commonly occurs in humans with peripheral edema of the lower legs

Phase-dependent roles of E-selectin during chronic contact hypersensitivity responses.

金沢大学大学院医学系研究科血管分子科学Chronic contact hypersensitivity (CH) models induced by repeated hapten exposure exhibit chronic dermatitis and immunological abnormalities resembling atopic dermatitis. To assess the contribution of endothelial selectins (P- and E-selectins) to cutaneous chronic inflammation, chronic CH responses were assessed in mice lacking P- or E-selectin. Elicitation with oxazolone on the ears of P-selectin(-/-) mice 7 days after the sensitization induced a typical delayed-type hypersensitivity response similar to that found in wild-type mice. By contrast, a significant increase in ear swelling was observed in E-selectin(-/-) mice 36 to 48 hours after first elicitation. E-selectin(-/-) mice showed augmented P-selectin up-regulation, and administration of anti-P-selectin monoclonal antibody significantly inhibited the enhanced ear response, suggesting that the enhanced ear-swelling response in E-selectin(-/-) mice resulted from compensatory increase in P-selectin expression. In the late phase of chronic CH, acceleration of ear swelling was significantly reduced in both E- and P-selectin(-/-) mice relative to wild-type littermates. Thus, the loss of P- or E-selectin suppressed inflammatory responses during the chronic phase of the chronic models, whereas early-phase inflammatory responses were exacerbated by E-selectin blockade. Collectively, P- and E-selectins cooperatively regulate CH response, although their roles may be different depending on the phase of the reaction

The involvement of Gab1 and PI 3-kinase in β1 integrin signaling in keratinocytes

金沢大学大学院医学系研究科血管分子科学The control of the stem cell compartment in epidermis is closely linked to the regulation of keratinocyte proliferation and differentiation. β1 integrins are expressed 2-fold higher by stem cells than transit-amplifying cells. Signaling from these β1 integrins is critical for the regulation of the epidermal stem cell compartment. To clarify the functional relevance of this differential expression of β1 integrins, we established HaCaT cells with high β1integrin expression by repeated flow cytometric sorting of this population from the parental cell line. In these obtained cells expressing β1 integrins by 5-fold, MAPK activation was markedly increased. Regarding the upstream of MAPK, Gab1 phosphorylation was also higher with high β1 integrin expression, while Shc phosphorylation was not altered. In addition, enhanced phosphatidylinositol 3-kinase activation was also observed. These observations suggest that Gab1 and phosphatidylinositol 3-kinase play pivotal roles in the β1 integrin-mediated regulation of the epidermal stem cell compartment. © 2007 Elsevier Inc. All rights reserved

Positive nasal culture of methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for surgical site infection in orthopedics

Background Although nasal carriage of MRSA has been identified as one of the risk factors for surgical site infection (SSI) with MRSA, there have been no reports of this in the orthopedics field

Relationship between Bone Mineral Density and Body Composition Estimated by Dual-Energy X-ray Absorptiometry : Comparison between Groups Aged 20-39 and 40-59 Years

Bone mineral density (BMD) is affected by lean body mass and body weight to various degrees in the course of aging. The attempt of this study is to determine the optimal time to begin prevention of osteoporosis. In this study, female hospital employees aged 20-59 years were divided into 2 age groups, 20-39 years and 40-59 years based on age at peak BMD, and the relations of total BMD, subtotal BMD and lumbar spine BMD to lean body mass and body weight were examined in both groups. Subtotal BMD was calculated by subtracting head BMD from total BMD along with whole body measurement. While persistent positive correlations were found among all factors in the 20-39-year-old group, subtotal BMD and lumbar spine BMD were positively correlated to lean body mass in the 40-59-year-old group. Thus, lean body mass and body weight appeared to exert a profound influence on subtotal BMD in those aged 20-39 years, but lean body mass in those aged 40-59 years. Lean body mass appears to provide the best prediction of subsequent development of osteoporosis