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K D Cooper

Publications and source records attributed to K D Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1996

Temporal correlation between UV radiation locally-inducible tolerance and the sequential appearance of dermal, then epidermal, class II MHC+CD11b+ monocytic/macrophagic cells.

We performed a time course study in order to define the in vivo relationship between the induction of active suppression of contact sensitization and the presence of various cells in ultraviolet-exposed dermis and epidermis implicated in locally inducible immune tolerance: class II major histocompatibility complex (MHC)+CD11b(lo)Gr-1- Langerhans cells (LC), class II MHC-CD45+CD3+ dendritic epidermal T cells, class II MHC+CD11b+Gr-1- monocytes or class II MHC+CD11b+Gr-1+ monocytic/macrophagic cells. Partial tolerance (50%) was first detectable 6 h after a single 72 mJ/cm2 ultraviolet B exposure and maximum tolerance at 48 h post-ultraviolet exposure. By flow cytometry, a low granularity LC subset had disappeared from the epidermis within 6 h after ultraviolet exposure, followed by a slower decrease in the high granularity Langerhans cells subset. Within the dermis at the 6-h time point, small numbers of infiltrating monocytic/macrophagic cells are already apparent. By 24 h post-ultraviolet exposure, at which time tolerance has increased to 70%, the infiltrating monocytic/macrophagic population had risen to 1.2% of the total dermal cell population and was observed for the first time in the epidermis along with other infiltrating leukocytes (i.e., polymorphonuclear leukocytes). By 48 h post-ultraviolet exposure, when a state of maximum tolerance is obtained, both constitutive epidermal and dermal antigen-presenting cell populations were at or near their nadir of depletion. The infiltrating monocyte/macrophage population, however, exhibited a dramatic increase in the epidermis at 48 and 72 h. Thus, the ability to locally induce a state of in vivo tolerance is closely associated with the expansion of class II MHC+CD11b+Gr-1+ and -monocytic/macrophagic cells in the dermis and epidermis.

Animals↗
PubMed1996

Differential regulation of IL-1 and IL-1 receptor antagonist in HaCaT keratinocytes by tumor necrosis factor-alpha and transforming growth factor-beta 1.

Cytokines such as TNF alpha and TGF beta 1 have potent effects on keratinocyte differentiation and have been implicated in cutaneous injury, immunologic reactions, and wound healing. To determine whether such conditions might alter the balance of epidermal keratinocyte IL-1 and the IL-1 receptor antagonist (IL-1ra), TNF alpha and TGF beta 1 were added to HaCaT cells, a human adult keratinocyte cell line. mRNA levels of IL-1 alpha, IL-1 beta, and IL-1Ra were detected by polymerase chain reaction (PCR) on reverse transcribed RNA extracts, followed by Southern blot of the PCR products, 35S-labeled probe hybridization, and quantification against standard curves. TNF alpha (100 ng/ml) at the 3-h time point significantly induced increases in mRNA expression of II-1 alpha (9.2 +/- 2.9 fold increase) and IL-1 beta (2.5 +/- 0.7 fold increase) (n=7) which were concordant with increases in IL-1 alpha protein (7.1 +/- 1.3 fold increase) and Il-beta protein (4.4 +/- 1.0 fold increase) measured by ELISA 24 h after stimulation. By contrast, icIL-1Ra mRNA and protein levels were not affected by TNF alpha. TGF beta 1 induced a mild increase in IL-1 alpha mRNA (3.8 +/- 1.8 fold) and protein (3.5 +/- 1.2 fold). TGF beta 1 did not affect IL-1 beta mRNA levels but caused variable increases in IL-1 beta protein levels. TGF beta 1 did not alter icIL-1Ra mRNA or protein levels. Inhibition of RNA synthesis with actinomycin D demonstrated that the rate of degradation of IL-1 beta mRNA was reduced by treatment with TNF alpha. This stabilization of IL-1 beta mRNA was specific, because TGF beta 1 did not stabilize IL-1 beta mRNA, and TGF beta 1 and TNF alpha did not increase the stability of Il-1 alpha mRNA. icIL-1Ra mRNA was fairly stable over a 20 hour period and its slow degradation was not affected by treatment with either TNF alpha or TGF beta 1, indicating a higher steady state stability of icIL-1ra mRNA relative to IL-1 mRNA's. Given the high rate of degradation of IL-1 alpha and IL-1 beta mRNA, levels of these mRNAs may rapidly decrease while the icIL-1ra mRNA levels remain constant, thus allowing for rapid dampening of IL-1 activity soon after the stimuli provoking an inflammatory or reparative response have abated. In conclusion, TNF alpha and TGF beta 1, cytokines with potent effects on inflammation and differentiation, both induce keratinocyte IL-1 alpha mRNA and protein levels, but differentially regulate IL-1 beta mRNA. They both exert little effect on IL-1 Ra levels, which were constitutively highly stable. Such differential regulation provides mechanisms for separately controlling the relative activity of these cytokines under normal and disordered conditions.

Adult↗
PubMed1996

Expression, but lack of calcium mobilization by high-affinity IgE Fc epsilon receptor I on human epidermal and dermal Langerhans cells.

In atopic dermatitis (AD) patients, IgE molecules are demonstrated on the surface of Langerhans cells (LC). Fc epsilon RI molecules, which are present on the surface of LC in AD patients as well as normal individuals, are responsible for this binding. In this study, we have investigated phenotypic and functional characteristics of Fc epsilon RI on epidermal and dermal cell populations. Epidermal and dermal cell suspensions were prepared enzymatically with dispase followed by either trypsin or collagenase treatment, respectively. Peripheral blood basophils were negatively selected by excluding other leukocytes with surface marker staining. Consistent with previous reports, both peripheral blood basophils and epidermal LC were positively stained with anti Fc epsilon RI monoclonal antibody. In addition, an Fc epsilon RI positive population was demonstrated among dermal HLA-DR positive cells. These cells express significant amounts of HLA-DR molecules (DRHi) and co-express CD 1 a molecules, which identifies them as LC-like dendritic APC of the dermis. No other Fc epsilon RI positive population was found in the other dermal DRMid or DR- populations, except for a minor DRLo population, presumably mast cells. To analyze whether these Fc epsilon RI molecules are signal transducing for LC, intracellular calcium mobilization after crosslinking of Fc epsilon RI was measured with flow cytometry. Following crosslinking, peripheral blood basophils clearly increased intracellular calcium. On the other hand, neither normal epidermal LC nor dermal DRHiCD1a + cells changed their intracellular calcium level after Fc epsilon RI crosslinking. These data indicate that normal epidermal and dermal LC, but not basophils, are resistant to calcium flux following Fc epsilon RI engagement.

Adult↗
PubMed1996

Cell-mediated immunosuppressive mechanisms induced by UV radiation.

Soon after UV exposure, mast cells degranulate, possibly because of the release of the mediators and cytokines from the epidermis, and there are subsequent vascular changes and cellular infiltration. Within a few hours, the soluble mediator milieu of UV-exposed skin becomes exceedingly complex and replete with interactions. Leukocytes newly entering the skin, as well as those already in the skin, must respond to these inflammatory signals. Altered antigen presentation and immune suppression likely derive from alterations induced in the APC that comprise the post-UV leukocyte population of the skin. Many of these mechanisms may explain the effectiveness of phototherapy in atopic dermatitis and psoriasis.

Animals↗
PubMed1996

Restructuring dermatology education at Cleveland medical centers affiliated with Case Western Reserve University.

We describe our response to the changing needs for dermatologic education and training at Cleveland medical centers affiliated with Case Western Reserve University School of Medicine (CWRU) located in Cleveland, Ohio. Our departmental plan for change is a multifaceted approach that alters the number of dermatology residents we train and also the way we interact with and educate our generalist colleagues. Like many other dermatologists, we have both idealistic and practical reasons for increasing our involvement in interdisciplinary education. One of our primary objectives is maximizing quality of care for dermatologic patients in our community. Traditionally, the majority of skin care in the United States has been provided by nondermatologists, and with the growth of managed care, this proportion is increasing. This has motivated us to increase our medical student teaching activities and to support the American Academy of Dermatology in its current efforts to develop a dermatology core curriculum for students. We should also be involved in the education of generalist physicians, since prior studies have suggested that their knowledge of dermatology needs improvement. Our goals should be both to improve the direct patient care skills of primary care physicians and to teach clinically appropriate referral thresholds. The American Academy of Dermatology has recently issued guidelines for the referral of dermatology patients in managed care settings to help ensure that our specialty has input into this process. In addition, teaching gatekeeper physicians to use appropriate referral criteria is important to many dermatologists in capitated managed care systems who often prefer limited as opposed to unrestricted access to their services.

Curriculum↗
PubMed1995

Suppressor T cell-activating macrophages in ultraviolet-irradiated human skin induce a novel, TGF-beta-dependent form of T cell activation characterized by deficient IL-2r alpha expression.

Because UV-induced epidermal macrophages (UV-Mph) preferentially activate CD4+ T suppressor-inducer cells and induce tolerance, we hypothesized that they differentially up-regulate T cell early activation genes compared with constitutive epidermal APC, Langerhans cells. We used epidermal cells from UV-exposed (UV-EC) and control (C-EC) human skin to stimulate allogeneic CD4+ T lymphocytes. Reverse transcriptase-PCR revealed that both C-EC (Langerhans cells) and UV-EC (UV-Mph) induced 10(3)- to 10(6)-fold increases in IL-2 mRNA. However, while T cells stimulated by C-EC for 48 h showed a greater than 10(3)-fold increase in IL-2R alpha mRNA, those stimulated by UV-EC did not (n = 5, p = 0.004). Flow cytometry demonstrated that 4.1 +/- 2.3% of unstimulated CD4+ lymphocytes expressed cell surface IL-2R alpha, which increased to 15.7 +/- 1.8% upon stimulation by C-EC for 48 h, but stimulation by UV-EC failed to increase the IL-2R alpha+ population (n = 3, p = 0.038). The addition of neutralizing anti-TGF-beta Abs to UV-EC-stimulated cultures restored CD4+ cell surface IL-2R alpha expression to 12.9 +/- 0.2%. CD4+ T cell activation by UV-Mph is distinct from previously described models of tolerance such as Th2 activation (IFN-gamma mRNA was induced and IL-4 mRNA was not) and Th1 anergy (IL-2 mRNA levels induced by UV-EC and C-EC were similar). Furthermore, costimulatory signals were provided by UV-Mph; CTLA4-Ig and LFA-3-Ig fusion proteins and Abs to CD2, LFA-3, LFA-1, and ICAM-1 inhibited UV-Mph-induced T cell proliferation. Thus, the altered immune outcome induced by UV-Mph (tolerization) compared with Langerhans cells (sensitization) is reflected as a novel mechanism of initial CD4+ T cell early activation gene expression characterized by TGF-beta-dependent deficient IL-2R alpha expression.

Antigen-Presenting Cells↗
PubMed1995

A clinical and histologic mycosis fungoides simulant occurring as a T-cell infiltrate coexisting with B-cell leukemia cutis.

One year after the onset of chronic lymphocytic leukemia, an elderly man had scaly cutaneous plaques on the thighs that clinically and histologically resembled the mycosis fungoides type of cutaneous T-cell lymphoma. Two years later the patient had indurated, red dermal nodules on the face that clinically and histologically were characteristic of cutaneous chronic lymphocytic leukemia. Immunophenotyping results from a facial nodule confirmed the presence of a B-cell infiltrate (CD20+). Immunophenotyping of a lesion on the right thigh showed that half the cells were composed of a CD2+, CD45RO+ (UCHL-1+) upper dermal and focally epidermotropic population of T cells consistent with mycosis fungoides; however, these T cells coexisted with an equal number of CD20+ B cells arranged in distinct clusters. DNA from the thigh lesion exhibited a B-cell immunoglobulin gene rearrangement, but the T-cell receptor gene rearrangements were germline. In this case, the evidence favors a mycosis fungoides simulant occurring as a reactive T-cell infiltrate to an underlying B-cell chronic lymphocytic leukemia.

Aged↗
PubMed1995

Antigen presenting cell-independent cytokine and spontaneous in vitro IgE production in patients with atopic dermatitis: increased interferon-gamma production and lack of effects of in vivo low-dose interferon-gamma treatment.

Atopic dermatitis is characterized by elevated serum IgE concentrations and dysregulation of T-lymphocyte function. To examine the pattern of cytokine production associated with elevated IgE levels, phorbol ester plus ionomycin-stimulated production of interleukin (IL)-4, IL-5, and interferon-gamma (IFN-gamma) by blood mononuclear cells from 16 patients with atopic dermatitis was compared with that of 18 healthy subjects. Spontaneous in vitro IgE production was also studied longitudinally in patients receiving placebo or daily treatment with 0.05 mg/m2 IFN-gamma. Spontaneous in vitro IgE production and mitogen-driven IL-4 and IFN-gamma synthesis did not differ when patients were receiving interferon treatment compared with no treatment. Furthermore, ionomycin plus phorbol ester-stimulated mononuclear cells from patients with atopic dermatitis produced less IL-4 and more IFN-gamma than did cells from healthy subjects. IL-5 production by cells from patients with atopic dermatitis did not differ from that of cells from healthy subjects. The ratio of IL-4 to IFN-gamma produced in vitro was significantly lower (p = 0.04) in the cells of patients with atopic dermatitis (0.9) as compared with those of healthy subjects (2.7). The findings suggest that when circulating T cells are stimulated under antigen presenting cell-independent conditions, atopic dermatitis is not characterized by the shift in the reciprocal relationship between IL-4 and IFN-gamma production, which has been postulated to explain the pathogenesis of IgE elevation and the therapeutic action of IFN-gamma in patients with atopic dermatitis.

Adult↗
PubMed1995

Intralesional T-lymphocyte activation as a mediator of psoriatic epidermal hyperplasia.

An early cellular event in the development of psoriatic lesions is infiltration of target tissue by macrophages and activated T lymphocytes. Lesional psoriatic skin contains activated memory T lymphocytes with production of mRNA for lymphokines such as interleukin-2, interferon-gamma, and tumor necrosis factor-alpha that is elevated relative to normal or uninvolved psoriatic skin. That the T-cell activation and cellular lymphokine production have a crucial role in the maintenance of epidermal hyperplasia in the psoriatic lesion is indicated by the beneficial effect of immunosuppressive agents in the treatment of psoriasis (cyclosporin A, FK506, anti-CD3, anti-CD4). A link between immune activation and psoriasis is also indicated by immunogenetic associations in this disease. Also, psoriatic keratinocytes appear to have been modulated by T-cell lymphokines in vivo, because they abnormally express molecules uniquely induced on keratinocytes by the T-cell product interferon-gamma. Indeed, T cells producing interferon-gamma have been cloned from psoriatic lesions, and they are able to induce keratinocyte class II major histocompatibility complex and intercellular adhesion molecule expression. These lesion-derived T-cell clones can induce growth of keratinocytes, and specifically lesional psoriatic T cells produce factors that induce increased keratinocyte colony formation, as well as increased cell cycle entry of the normally quiescent stem cell population. Interferon-gamma, although a growth inhibitor on its own, acts cooperatively with other T-cell-produced growth factors to cause keratinocyte growth induction. Furthermore, relative to normal stem cells, keratinocyte stem cells (beta 1 integrin+ K1/K10-) in psoriatic uninvolved epidermis are significantly hyperresponsive to the growth-stimulatory lymphokine milieu created by lesional T lymphocytes. Whether such abnormalities in responsiveness are associated with new genetic linkages reported in families of psoriasis patients is unknown. As the epidermis of lesional psoriatic skin can be demonstrated to produce elevated levels of factors that can further potentiate T-cell activation, a self-sustaining cycle can be constructed of T-cell recruitment, intralesional activation, release of factors that preferentially stimulate psoriatic epidermal stem cells to proliferate, and further epidermal potentiation of the T-cell-mediated lesions.

Animals↗
PubMed1995

Differential extracellular signaling via Fc gamma R and FMLP in functionally distinct antigen-presenting cell subsets: ultraviolet-induced epidermal macrophages versus Langerhans cells.

Sunburned skin is characterized by expanded numbers of macrophages (ultraviolet [UV]-MPH), and these UV-MPH differ from Langerhans cells (LC) in their abilities to initiate T-cell-mediated immune reactions. UV-MPH and LC may themselves be differentially responsive to the surrounding milieu, which may in turn modulate their immunoregulatory activity. We asked whether immunologic signal responsiveness, as assessed by cytosolic calcium mobilization, differed among normal human LC, UV-MPH, and normal blood monocytes. LC from normal skin and UV-MPH from UV-exposed skin were distinguished from keratinocytes in epidermal cell suspensions by labeling with anti-HLA-DR. Intracellular calcium content was monitored in real time with the calcium indicator, indo-1, after cross-linking Fc gamma RI, Fc gamma RII, CD11b, CD11c, or CD18 molecules, or addition of interleukin-1 alpha, IL-1 beta, interferon-gamma, bradykinin, substance P, or FMLP. Using flow cytometric analysis of cell suspensions, UV-MPH and blood monocytes were triggered by cross-linking Fc gamma RII (flux of 6.05 and 12.2, respectively). UV-MPH could also be triggered by Fc gamma RI crosslinking and FMLP (flux of 6.41 and 15.54, respectively). By contrast, none of these inflammatory stimuli could cause cytosolic calcium mobilization in normal LC (Flux of -0.2 by FcRII, and 0.18 by FMLP). Because LC calcium flux may be dependent upon extracellular attachments, LC were anchored onto fibronectin-coated coverslips and then their Fc gamma RII was crosslinked in a continuous flow chamber. However, image analysis also failed to detect calcium flux. Neither population responded to interleukin-1, interferon-gamma, bradykinin, substance P, or beta 2 integrin crosslinking. These results indicate that blood monocytes and infiltrating macrophages differ substantially from LC in their responses to immune complexes and chemoattractants. Differential responsiveness to the inflammatory milieu may influence the antigen presenting or effector capabilities of these populations.

Antigen-Presenting Cells↗
PubMed1995

In human dermis, ultraviolet radiation induces expansion of a CD36+ CD11b+ CD1- macrophage subset by infiltration and proliferation; CD1+ Langerhans-like dendritic antigen-presenting cells are concomitantly depleted.

Antigen-presenting (APC), suppressor T-cell-inducing macrophages infiltrate both human and murine epidermis after ultraviolet radiation (UVR) exposure. To determine their derivation, we prepared epidermal cell and dermal cell suspensions from human keratome biopsy specimens obtained from nonexposed skin and from UVB-irradiated sites (3 d after four times the minimal erythema dose). Simultaneous triple-marker flow cytometric analysis established the extended phenotype of macrophages infiltrating sunburned human epidermis (CD1a- CD1c- CD11b+ CD11c+ CD36+ Fc gamma RII+ DR+). This then enabled us to track dermal cells of this phenotype after UVR in relation to the heterogeneous DR+ populations in normal dermis. By both in situ immunohistology and cell suspension flow cytometry, UVR induced an expansion of bone marrow-derived DR+ cells in the perivasculature and sub-basement membrane zone of the papillary dermis. Despite an overall expansion of DR+ cells, the CD1a+ CD1c+ CD36- DR+ Langerhans-cell-like dendritic APC subset of dermal DR+ cells was depleted (p < 0.05), indicating that UVR-induced epidermal Langerhans cell loss (from 95% to 7% of DR+ epidermal cells) is not accounted for by Langerhans cell accumulation in the dermis. By contrast, UVR exposure induced a selective expansion of the dermal macrophage subset, which is phenotypically identical to the monocytic/macrophagic APCs that appear in the epidermis after UV injury (p < 0.01). Cell cycle analysis (to determine whether this expansion was accounted for entirely by infiltration) revealed no increase in the percentage of DR+ CD36+ UVR-exposed dermal cells in S/G2/M phase; however, the expanded DR+ CD36+ subset continued its already substantial level of proliferation unabated. Therefore, epidermal macrophages derive not only from transcapillary migration, but also from in situ proliferation of a dermal precursor. Taken together, these findings show that UVR creates an epidermal and dermal APC milieu which is dominated by monocytic/macrophagic cells, through depletion of cells of dentritic APC phenotype, and concomitant selective dermal expansion of a CD1a- CD1c- CD11b+ CD36+ Fc gamma RII+ DR+ (monocyte/macrophage) population.

Adult↗
PubMed1995

Differential responsiveness of Langerhans cell subsets of varying phenotypic states in normal human epidermis.

Epidermal Langerhans cell heterogeneity is poorly understood with regard to phenotypic characteristics, such as the expression of human leukocyte antigen (HLA)-DR, integrin, and Fc receptor molecules, as well as functional characteristics, such as the ability to process and present antigens or produce cytokines during various phases of immigration and maturation. Technical limitations of Langerhans cell number have limited functional assays on putative Langerhans cell subsets in in vivo epidermis. Therefore, we used flow cytometry for simultaneous phenotypic and functional assessment at the single-cell level within the Langerhans cell population. Freshly isolated human epidermal cell suspensions were stained with a battery of monoclonal antibodies, including anti-HLA-DR, -CD1a, -CD1c, -CD11c, -Fc gamma RII, and -Fc epsilon RI. Two distinct Langerhans cell subsets were identified by their different levels of HLA-DR expression. The DRHi subset expressed higher amounts of CD11c and exhibited greater cytoplasmic complexity and higher baseline calcium than the DRLo subset (p < or = 0.03 for each). Some subjects also expressed high levels of Fc epsilon RI in the DRHi, CD11cHi subset. To determine whether these phenotypic subsets may exhibit differential signal-transduction functional properties, Langerhans cells were partially enriched over Ficoll-Hypaque and their cytosolic mobilization after the addition of ionomycin was analyzed using the calcium indicator, indo-1, in conjunction with quantitative analysis of HLA-DR expression. By this real-time flow cytometric analysis, a new subpopulation was revealed within the DRLo Langerhans cell subset. This subset increased its cytosolic calcium concentration much more than the other two subsets (change in indo-1 blue:violet emission ratio of 37.33 +/- 2.34 in the Hi Flux DRLo subset versus 13.23 +/- 0.29 in the Lo Flux DRLo subset, and versus 7.6 +/- 2.99 in the Lo Flux DRHi subset). These data indicate that functional, as well as phenotypic, subsets of Langerhans cells exist within normal human epidermis. Their responses to physiologic stimuli may relate to maturational stage or the level of in vivo activation.

Adult↗
PubMed1995

Defective in vivo expression and apparently normal in vitro expression of a newly identified 105-kDa lower lamina lucida protein in dystrophic epidermolysis bullosa.

We have previously identified a novel 105-kDa lower lamina lucida protein detected by the autoantibodies from a group of patients who developed a unique immune-mediated subepidermal bullous dermatosis. We sought to determine if this novel basement membrane zone (BMZ) protein is normally expressed in the skin of patients with various subsets of epidermolysis bullosa (EB). Indirect immunofluorescence microscopy performed on non-lesional skin sections from patients with three major EB subsets revealed absence or significantly reduced expression of this novel BMZ protein in 20 out of 23 skin sections from patients with generalized dominant and recessive dystrophic EB. However, immunoblot analyses with the autoantibodies on Western-blotted proteins revealed that a comigrating 105-kDa protein is present in both cytosol extracts (n = 6) and conditioned media (n = 3) of cultured dermal fibroblasts derived from patients with dystrophic EB, as well as those cultured from two healthy individuals. Although the reason for such disparate findings is not known, the defective in vivo expression of this novel 105-kDa protein in dystrophic EB is presumably not due to a failure of fibroblasts to synthesize or secrete the protein. It is possible, however, that the 105-kDa protein may be unable to incorporate into the BMZ because it is produced in a dysfunctional form, or its BMZ binding site is missing. It is also possible that other structural alterations in skin BMZ, which occur in dystrophic EB, result in masking of the antigenic binding by the autoantibody when intact BMZ is probed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Down-regulation of Langerhans cell protein kinase C-beta isoenzyme expression in inflammatory and hyperplastic dermatoses.

The family of protein kinase C (PKC) isoenzymes plays a fundamental part in signal transduction, and thereby regulates important cellular functions, including growth, differentiation, cytokine production and adhesion molecule expression. In lesional psoriatic skin, Ca(2+)-dependent PKC activity, PKC-beta protein and epidermal Langerhans cell (LC) PKC-beta immunostaining are significantly decreased, indicating activation and subsequent down-regulation of PKC. Whether these changes occur in other inflammatory/hyperplastic dermatoses is, however, unknown. We examined PKC-alpha and PKC-beta expression in normal skin, psoriasis, cutaneous T-cell lymphoma (CTCL), lamellar ichthyosis, non-bullous ichthyosiform erythroderma, atopic dermatitis, urushiol-induced allergic contact dermatitis, and sodium lauryl sulphate (SLS)-induced irritant contact dermatitis. Cryostat sections were stained for PKC-alpha and PKC-beta, and the LC marker CD1a, using an immunoperoxidase technique and specific monoclonal antibodies. Double-labelling studies, in normal skin, revealed co-expression of PKC-beta and CD1a by epidermal LCs. Analysis of the number of PKC-beta+ and CD1a+ epidermal LCs, in diseased compared with normal skin, revealed three categories: (i) in psoriasis and CTCL, the PKC-beta+ epidermal LC number was significantly reduced, whereas the CD1a+ epidermal LC number was unchanged; (ii) in allergic and irritant contact dermatitis, both PKC-beta+ and CD1a+ epidermal LCs were significantly reduced in number; and (iii) in atopic dermatitis, the PKC-beta+ epidermal LC number was normal, and CD1a+ epidermal LCs were significantly increased in number. Moreover, the ratio of epidermal LC PKC+/CD1a+ was reduced in all the dermatoses studied, suggesting activation of PKC-beta, with subsequent down-regulation. Within the dermis, increased PKC-beta staining of infiltrating cells was observed in all the conditions studied except lamellar ichthyosis and non-bullous ichthyosiform erythroderma. These data indicate that: (i) down-regulation of LC PKC-beta occurs in a variety of inflammatory and hyperplastic skin disorders, and is not unique to psoriasis, and (ii) the pattern of epidermal LC PKC-beta and CD1a expression varies among the diseases studied. In mice, PKC activation induces LC migration. Thus, down-regulation of epidermal LC PKC-beta associated with reduced CD1a+ epidermal LCs in allergic and irritant contact dermatitis suggests that PKC-beta may transduce the signal for migration of LCs from human epidermis.

Adult↗