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Biomedical subjects

R L Baer

Publications and source records attributed to R L Baer.

At least 19 recordsLinked to original sources
PubMed1991

Immunosuppressive effects of transforming growth factor beta: inhibition of the induction of Ia antigen on Langerhans cells by cytokines and of the contact hypersensitivity response.

Recent reports show that transforming growth factor (TGF)-beta exerts a variety of immunosuppressive activities. The present study focuses on the effects of TGF-beta 1 on expression of Ia antigen by Langerhans cells. Although TGF-beta 1, in concentrations from 0.001 to 100 micrograms/ml, has no effect on constitutive expression of Ia antigen on these cells, the in vitro up-regulation of Ia antigen on the surface of LC by interleukin (IL)-1, tumor necrosis factor-alpha, interferon-gamma, IL-3, and granulocyte/macrophage-colony stimulating factor is inhibited by the concomitant addition of 1 microgram/ml TGF-beta 1. In contrast, TGF-beta 1 has no effect on the up-regulation induced by IL-2 or IL-6. In this report, the activity of TGF-beta closely resembles that of Cyclosporine A (CsA). Similar results are seen in vivo when either TGF-beta 1 (5 micrograms, intraperitoneally [ip], daily on days 0-3) or CsA (1 mg, subcutaneously [sc], twice daily on days 0-3) are given together with IL-2 (500 U, intraperitoneally [ip], twice daily on days 1-3) or interferon-gamma (4,000 U, ip, twice daily on days 1-3). Given the important role of Ia expression in cell-mediated immune reactions, the effect of TGF-beta on contact sensitivity was next investigated. In doses of 5 micrograms, ip, daily on days 6-8, TGF-beta inhibits the expression of contact reactivity in animals sensitized on day 0 and challenged on day 7. In contrast, no effect is observed on the induction of contact sensitivity in mice given TGF-beta 1 on days--1 to 2, sensitized on day 0, and challenged on day 7. The possible importance of antagonism between TGF-beta and other cytokines, especially IFN-gamma, involved in the elicitation of contact hypersensitivity reactions is discussed.

Animals↗
PubMed1991

Effect of triggering epidermal Fc gamma receptors on the interleukin-2- and interleukin-6-induced upregulation of Ia antigen expression by murine epidermal Langerhans cells: the role of prostaglandins and cAMP.

Following incubation of murine epidermis in medium containing either interleukin-2 or interleukin-6, there is significant upregulation in the density of Ia+ epidermal Langerhans cells (to 159% and 175% of control, respectively). This cytokine-induced upregulation is abrogated by either rabbit or human IgG due to triggering of Fc gamma receptors. In contrast, human IgA does not inhibit the effect of interleukin-2 or interleukin-6. Using different isotypes of murine IgG, we have demonstrated that all subclasses are capable of inhibiting the cytokine-induced enhancement of Ia antigen, although IgG1 and IgG2b must be heat aggregated to be effective. The IgG-mediated events are dependent on prostaglandin synthesis because they can be blocked by the cyclooxygenase inhibitor indomethacin, 10 micrograms/ml. The responsible PG appears to be PGD2; in contrast to its known inhibitory effect on macrophages, PGE2 does not inhibit the upregulation of Ia antigen on Langerhans cells. In addition, these IgG-mediated events are dependent upon the generation of cAMP because they can be blocked by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine, 1 mM. Despite the apparently central role of PGD2 and cAMP in this process, triggering of the Fc gamma R by different isotypes of IgG blocks upregulation of Ia via at least two different pathways. The inhibition caused by aggregated IgG1 or IgG2b, which bind to Fc gamma RII on Langerhans cells, is abrogated by para-bromophenacylbromide, an inhibitor of phospholipase A2. In contrast, the inhibition caused by monomeric IgG2a, which binds to Fc gamma RI most likely on keratinocytes, or monomeric IgG3, which probably binds to this same Fc gamma RI, is abrogated by staurosporine, an inhibitor of protein kinase C, as well as by W7, a calmodulin antagonist. Finally, 1,2 dioctanoyl-rac-glycerol, an activator of protein kinase C, mimics the Ig-mediated events. Based on these findings, as well as studies using monoclonal antibodies to the murine Fc gamma receptors I and II, we conclude that, as is the case in murine macrophages, triggering of an epidermal Fc gamma RI, most likely on keratinocytes, results in the generation of cAMP via a Ca(++)-dependent protein kinase C pathway, whereas triggering of an epidermal Fc gamma RII, most likely on Langerhans cells, results in the elevation of cAMP via a phospholipase A2-mediated pathway. In contrast to the situation for macrophages, PGD2 is a vital intermediate in both pathways, perhaps because Langerhans cells have receptors for only this prostaglandin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Poison ivy dermatitis.

Eruptions caused by poison ivy and related plants are almost always a form of allergic contact dermatitis. Usually they can be readily recognized because of their characteristic streak-or-line-like appearance. They usually clear within one to three weeks unless there is continued exposure to the allergen. Local treatment suffices in mild to moderate cases, but in more severe cases systemic corticosteroids can be added.

Adrenal Cortex Hormones↗
PubMed1989

Enhancement by various cytokines or 2-beta-mercaptoethanol of Ia antigen expression on Langerhans cells in skin from normal aged and young mice. Effect of cyclosporine A.

The number of Ia+ Langerhans cells (LC) in skin from aged (16- to 18-mo old) BALB/c mice is approximately 40% lower than in skin from young (2- to 3-mo old) mice. Overnight incubation at 37 degrees C with a variety of cytokines, including IL-1, IL-2, IL-3, IL-4, IL-6, TNF-alpha, IFN-gamma, and granulocyte/macrophage-CSF, causes a significant increase in the Ia expression on LC and raises the number of Ia+ cells by at least 300/mm2 in skin from both young and old mice. At 1 to 5 x 10(-5) M, 2-ME has a similar effect. The percentage increment in Ia+ cells is much higher for skin from aged mice than from young mice, particularly with IL-3, which appears to reconstitute the number of Ia+ LC in skin from aged mice to that of IL-3 exposed skin from young mice. Under the incubation conditions of our experiments, neither keratinocytes nor Thy-1+ dendritic cells acquire Ia Ag. Addition of 10 micrograms/ml cyclosporine A to the medium abolishes the effect of 2-ME and of all of the cytokines except IL-2 and IL-6. These results demonstrate the presence of a significant population of Ia- LC in the epidermis of both young and aged mice. It is suggested that epidermal production of cytokines may be of importance in the maintenance of constitutive Ia expression on LC. The possible interaction between keratinocytes and LC and the effect of aging on this process are discussed.

Adjuvants, Immunologic↗
PubMed1989

The role of Langerhans cells in allergic contact hypersensitivity. A review of findings in man and guinea pigs. 1976.

Evidence in favor of a role for Langerhans cells in contact allergic hypersensitivity reactions has been reviewed. This includes mononuclear cell to Langerhans cell apposition and damage to some Langerhans cells at sites of specific challenge to a variety of contact allergens. Such apposition occurs in actively sensitized patients and guinea pigs and in passively sensitized guinea pigs. In addition, in passively sensitized guinea pigs, Langerhans cells circulate in dermal vessels resembling lymphatics and are much increased in the dermis after challenge with the contact allergen. These observations, together with the existing knowledge that Langerhans cells occur in the lymph nodes and thymus, suggest that these cells may be involved not only in contact allergic reactions but also in other immunologic reactions, particularly in cell-mediated reactions in the skin.

Animals↗
PubMed1988

Relative lack of systemic effects of mometasone furoate on Langerhans cells of mice after topical administration as compared with other glucocorticosteroids.

The effects of topically applied mometasone furoate were compared with those of other glucocorticosteroids, in particular fluocinolone acetonide, in assays of murine epidermal Ia+ Langerhans cell density. No evidence of systemic effects, as determined by a decline in the density of Ia+ LC in distant sites, was detected after local topical applications (5 times a week) of mometasone furoate 0.001% for periods of up to 3 weeks. Other steroids, even in such very low concentrations, and mometasone furoate in higher concentrations, produced systemic effects on Ia+ LC when used for longer than 5 d. The recovery time of Ia+ Langerhans cells is significantly shorter after application of mometasone furoate than after fluocinolone acetonide. However, with both compounds, recovery occurred more rapidly after 3 weeks than after a 1- or 2-week interval of compound administration.

Administration, Topical↗
PubMed1987

Reversal by lymphokines of the age-related hyporesponsiveness to contact sensitization and reduced Ia expression on Langerhans cells.

Contact sensitivity responses were evaluated in young adult (3-5 months) and aged (16-26 months) BALB/c mice which were systemically treated with interleukin-2 (IL-2), interferon-gamma (IFN-gamma) or saline. Mice older than 16 months of age have deficient numbers of Ia+ Langerhans cells in addition to their well-known impaired T cell functions. They also have an impaired cell-mediated response to contact sensitization with 1-chloro-2,4,6-trinitrobenzene. This hyporesponsiveness in aged mice can be almost completely reversed by IL-2 and is marginally improved by IFN-gamma. Exposure of skin from aged mice to interleukin-2 or interferon-gamma, both in vivo and in vitro, causes increases in the density of Ia+ Langerhans cells to levels approximating those in young mice. Since IFN-gamma causes partial restitution while IL-2 fully restores the contact hypersensitivity in aged animals, we conclude that the hyporesponsiveness in aged mice results both from defective Ia antigen expression on the antigen-presenting Langerhans cells and from deficient T cell function.

Age Factors↗
PubMed1987

Photodermatoses.

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Bibliographies as Topic↗
PubMed1986

Reversal by lymphokines of the effect of cyclosporin A on contact sensitivity and antibody production in mice.

Cyclosporin A (CsA) treatment of mice during the first 4 days of the sensitization phase prevents induction of contact sensitivity to trinitrochlorobenzene (TNCB). Administration of CsA on the day of ear challenge with TNCB also inhibits the effector phase of this response. Simultaneous treatment of the mice with IL 2-containing murine lymphokine preparations or with recombinant human IL 2 reverses the effect of CsA on the induction of contact sensitivity. Recombinant IL 2 also reverses the inhibition by CsA of the effector phase. Neither phase of the response is restored by murine IFN-gamma. Anti-body production to trinitrophenylated (TNP) Ficoll or TNP-hemocyanin is also strongly inhibited (greater than 75%) by CsA injected on the day of antigen injection. Although lymphokines or endotoxin may strongly enhance these responses, no reversal of the effect of CsA can be obtained. We conclude that inhibition of IL 2 production is of paramount importance for the inhibitory effect of CsA on contact sensitivity, but that additional effects are involved in the inhibition of antibody production to both T-dependent and T-independent antigens.

Animals↗
PubMed1986

Subepidermal vesicular dermatosis and sensory peripheral neuropathy caused by pyridoxine abuse.

A woman who had ingested 2 gm of pyridoxine (vitamin B6) daily for 2 years for menstrual water retention developed a subepidermal vesicular eruption on the dorsa of the hands and toes, as well as a sensory peripheral neuropathy. The cutaneous and neurologic manifestations subsided about 2 months after discontinuation of the pyridoxine. The possible relationship of subepidermal vesicular eruptions caused by pyridoxine abuse to epidermolysis bullosa acquisita is discussed.

Female↗
PubMed1986

Poison ivy dermatitis.

Eruptions caused by poison ivy (see Cover) and related plants are almost always a form of allergic contact dermatitis. Usually they can be readily recognized because of their characteristic streak- or line-like appearance. They usually clear within one to three weeks unless there is continued exposure to the allergen. Local treatment suffices in mild to moderate cases, but in more severe cases systemic corticosteroids can be added.

Acute Disease↗
PubMed1985

Syngeneic mixed lymphocyte reactions to murine Fc receptor-bearing, nonadherent low density lymph node cells and epidermal Langerhans cells.

Both Langerhans cells from BALB/c mouse epidermis and nonadherent, low density (LD) cells, obtained from collagenase-treated minced lymph node, are stimulatory for isolated T cells in syngeneic mixed lymphocyte reaction (SMLR). The method of preparation of LD cells influences whether Fc receptor (FcR) can be detected on them. Fc receptors on nonadherent LD lymph node cells can be detected only if the same procedure is employed as that for Langerhans cell isolation, i.e., Ig-free bovine albumin must be used during gradient centrifugation and EA rosetting must be done overnight at 4 degrees C. Thus, both FcR+ and FcR- LD lymph node cells, as well as FcR+ Langerhans cells, stimulate SMLR. Although Ig+ cells in the LD fraction also stimulate the SMLR, their removal does not affect the stimulating capacity of the LD lymph node fraction.

Animals↗
PubMed1985

Papaverine therapy in atopic dermatitis.

Papaverine hydrochloride taken by mouth in doses of 100 mg four to six times daily or in 150-mg timed-release capsules two or three times daily is often effective in significantly decreasing itching in patients with atopic dermatitis. When used orally, as described here, it does not appear to have beneficial effects in other itchy dermatoses. It should be used as adjuvant treatment in combination with other accepted forms of therapy, since it alone cannot reverse the chronic skin changes brought about by months or years of scratching and rubbing.

Adrenal Cortex Hormones↗