Recruitment of mononuclear cells by endothelial cell binding into wounded skin is a selective, time-dependent process with defined molecular interactions.
ABSTRACT Wound healing involves a complex series of interactions between cells in the dermis and epidermis, and important relationships exist between keratinocytes and resident dermal cells. Monocytes and lymphocytes secrete cytokines that are capable of stimulating dermal repair and influencing keratinocyte and fibroblast migration and proliferation, although the mechanism by which mononuclear cells are recruited into the wound is unknown. We have tested the hypothesis that in wounded skin specialized endothelial cells are induced to mediate peripheral blood mononuclear cell (PBMC) emigration from the vasculature into the dermis. For this purpose, partial-thickness wounds made with a keratome on the backs of domestic pigs were excised 0 to 9, 12, 15, and 21 d after wounding. The biopsies were then tested for the capacity to adhere selectively to PBMC. The results indicated that PBMC overlaid onto sections of wounds from day 4 to 15 adhered selectively to dermal endothelium, with two distinct peaks of adherence observed on day 7 and day 12. In contrast, PBMC did not adhere to the tissue sections when overlaid onto frozen sections of normal skin or 0-, 1-, 2-, 3-, and 21-d-old wounded skin. Additional studies on the binding properties of PBMC subsets revealed that monocytes adhered maximally at day 7, whereas T cells adhered optimally at day 12 post-wounding. Furthermore, the adhesion process was energy and magnesium dependent but not calcium dependent and involved surface protein and carbohydrate moieties on PBMC surface. Pre-treatment of PBMC with monoclonal antibodies against the LFA-1 adhesive receptors inhibited the binding by greater than 80%, suggesting that LFA-1 adhesive receptors play an important role in the binding process. These studies provide evidence that the recruitment of monocytes and lymphocytes into wounds is an active, dynamic, and regulated process mediated at least in part by specific adhesive interactions between mononuclear leukocytes and dermal endothelial cells.
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ABSTRACT: A dermal lymphocytic infiltrate is a characteristic feature of psoriasis, and may be involved in the pathogenesis of the disease. We have previously shown that specialized dermal microvascular endothelial cells (DMEC) in psoriatic lesions promote the selective adherence of the CD4 CD45Ro helper T-cell subset. In this study, we examined the adhesive interaction between peripheral blood mononuclear cells and psoriatic DMEC in patients treated with ultraviolet B light (UVB), and correlated the results with the expression and function of endothelial adhesion molecules on DMEC. Seven psoriatic patients were exposed to one MED of UVB daily for 14 days, and the binding properties of their peripheral blood mononuclear cells (PBMC), and tissue specimens taken from their lesions on days 0, 2, 3, 6, 8, 11 and 14 of UVB treatment, were studied. The ability of psoriatic PBMC to adhere to non-irradiated control or UVB-treated psoriatic plaques was reduced by 70% after treatment with 2-3 MED, and complete inhibition was obtained after 8-11 MED. In contrast, exposure of psoriatic plaques to 2-3 MED had no effect on the capacity of DMEC to support normal PBMC binding, which was only reduced after 8-11 MED. In addition, psoriatic plaques which were shielded from direct UVB exposure also showed decreased PBMC binding, suggesting a systemic effect of UVB treatment. Immunoperoxidase staining revealed that CD54 (ICAM-1) and E-selectin were strongly expressed on dermal vessels in untreated psoriatic plaques. Treatment of patients with 6-8 MED significantly decreased CD54 and E-selectin expression. In contrast, VCAM-1 expression on untreated plaques was weaker than that of CD54 and E-selectin, but was markedly induced following UVB treatment. In functional blocking studies, preincubation of tissue from untreated psoriatic plaques with anti-E-selectin antibody, but not antibodies against CD54 and VCAM-1, significantly inhibited the ability to bind normal PBMC. These observations suggest that UVB treatment interferes with the adhesive properties of both psoriatic PBMC and endothelial cells, and differentially regulates the expression of endothelial adhesion molecules. The study also provided direct evidence for the involvement of E-selectin in the adhesion of circulating lymphocytes to psoriatic endothelial cells.British Journal of Dermatology 02/1996; 134(1):7-16. · 3.76 Impact Factor
- Journal of Investigative Dermatology 06/1993; 100(5):721-5. · 6.19 Impact Factor
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ABSTRACT: To determine if weekly oral 2-chlorodeoxyadenosine (2-CdA) can induce selective lymphocytopenia, and reduce inflammation, in patients with refractory psoriatic arthritis. Seven patients with psoriatic arthritis were treated with oral 2-CdA at weekly dosages of 0.3 mg/kg to 0.45 mg/kg for 12 weeks, followed by monthly maintenance therapy. The patients were evaluated after 6 months. The drug treatment produced selective lymphocytopenia, and reduced lymphocyte infiltration into involved skin. One patient did not complete 12 weeks of therapy because of perceived lack of efficacy. Four of the 6 remaining patients had improved joint disease, and 5 of 6 had improved psoriasis. Weekly oral 2-CdA appears to be a well-tolerated regimen for the inducement of peripheral lymphocytopenia in patients with psoriatic arthritis. Larger-scale, controlled trials may be warranted.Arthritis & Rheumatology 12/1995; 38(11):1604-9. · 7.48 Impact Factor