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N Duraiswamy

Publications and source records attributed to N Duraiswamy.

8 recordsLinked to original sources
PubMed1996

Reversal of immunosuppression inducible through ultraviolet-exposed skin by in vivo anti-CD11b treatment.

In both human in vitro models and murine in vivo adoptive transfer studies, UV-induced class II MHC+ CD11b+ leukocytes that infiltrate the epidermis appear to mediate UV-induced immunosuppression. In the present study, their role is further probed using an anti-CD11b mAb (clone 5C6), which is effective in vivo in blocking CD11b+ monocyte/macrophage diapedesis into inflammatory lesions. A single exposure, low dose UV protocol (72 mJ/cm2) that resulted in tolerance only when dinitroflurobenzene was applied 48 h later through the UV-irradiated skin, but not through a distant non-UV-irradiated site, was used. In vivo anti-CD11b treatment in non-UV-irradiated mice did not block contact sensitivity responses. However, the ability to induce a primary contact sensitivity response was completely restored in UV-irradiated mice receiving anti-CD11b. This restoration was associated with partial restoration of papillary dermal class II MHC+ NLDC-145- cells. In vivo anti-CD11b treatment also blocked tolerance induction, which was associated with a 50% reduction in the infiltration of class II MHC+ CD11b+ Gr-1+ monocyte/macrophages into UV-irradiated skin. In addition, anti-CD11b treatment partially protected against epidermal UV injury, in that the epidermal structure was better preserved and the keratinocytes were less severely damaged. CD11b+ leukocytes may thus affect UV-irradiated skin through at least two mechanisms: 1) a class II MHC+ CD11b+ Gr-1+ monocyte/macrophage population inducing a state of tolerance to Ag(s) acquired in UV-irradiated skin, and 2) CD11b+ leukocytes capable of inflicting additional injury to both keratinocytes and constitutive APC damaged by UV photons.

Animals↗
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↗
PubMed1994

Active induction of unresponsiveness (tolerance) to DNFB by in vivo ultraviolet-exposed epidermal cells is dependent upon infiltrating class II MHC+ CD11bbright monocytic/macrophagic cells.

Contact sensitizers, tumor Ags, and microbial pathogens presented through UV-exposed skin result in T cell-mediated immune tolerance (inhibition of acquisition of responsiveness) to these normally potent immunogens. The APC in UV-exposed skin that delivers the signals inducing tolerance remains highly controversial and is the subject of this study. Application of the contact sensitizer, 2,4-dinitro-1-fluorobenzene (DNFB), to C3H/HeN mice immediately after a single dose of 72 mJ/cm2 UVB (138 mJ/cm2 total UVB) resulted in unresponsiveness to an initial DNFB ear challenge, but failed to block the development of responsiveness after a second sensitization on previously unexposed skin (no tolerance). A state of tolerance could only be achieved if a delay of 72 h was allowed to elapse between the UV exposure and the initial sensitization. Epidermal cell suspensions (EC) were prepared from the skin of normal controls and from skin exposed to the same UV dose 3 days before (UV-EC). Three days after in vivo UV exposure, Langerhans cells (CD11blow Ia+) were depleted, and CD11bbright Ia+ macrophages had appeared in the epidermis along with GR-1+ neutrophils. Intracutaneous injection of 2,4 dinitrobenzenesulfonic acid (DNBSO3)-haptenated UV-EC, but not normal controls, resulted in the induction of locally inducible Ag-specific tolerance to DNFB, indicating the presence and dominance of tolerogenic signal within in vivo-irradiated epidermis. Removal of CD11b+ and class II MHC+ cells within UV-EC showed that a CD11b+ class II MHC+ population was indeed critical for tolerance induction. In addition, tolerance induction by UV-EC was not a result of surviving, UV-exposed Langerhans cells, because haptenated 3-day cultured EC from epidermis removed 5 h after UV exposure (before leukocytic infiltration) failed to induce a tolerogenic state. In conclusion, the ability of UV-exposed skin to induce peripheral adult tolerance to a normally potent immunogen is critically dependent on inflammatory class II MHC+, CD11bbright monocytic/macrophagic cells that infiltrate UV-irradiated skin at the same time the ability to tolerize is acquired.

Animals↗
PubMed1994

Distinction of class II MHC+ Langerhans cell-like interstitial dendritic antigen-presenting cells in murine dermis from dermal macrophages.

Dermal cells are capable of initiating contact-hypersensitivity responses but the precise identification of the antigen-presenting cell within murine dermis is lacking. Class II major histocompatibility complex (MHC)+ cells with dendritic shape and lacking endothelial factor VIII but expressing the dendritic antigen-presenting cell marker NLDC-145 were observed in the perivascular and interstitial dermis of BALB/c and C3H/HeN skin. The heterogeneous class II MHC+ cells could be divided into two subsets: each was class II MHC+ CD45+ (bone marrow derived) GR-1- (non-neutrophil/macrophage) CD3- (non T), but one subset was CD11b+ (beta 2 integrin) and the other was CD11b-. Ultrastructural examination of class II MHC+ cells revealed the presence of a Langerhans cell-like/indeterminant cell subset with indented nuclei, dendritic morphology, active cytoplasm, and dense intermediate filaments. Phagolysomes and Birbeck granules were not observed in such cells, indicating these were distinct from dermal macrophages and from classical epidermal Langerhans cells, respectively. Cells with a monocyte/macrophage ultrastructural appearance were also noted, likely representing the class II MHC subset expressing CD11b and Ly6c (monocyte/endothelial antigen). Dermal cells in suspension were capable of processing and presenting large protein antigens to antigen-specific T-cell hybridomas; dermal cells also induced the syngeneic mixed lymphocyte reaction. The dermal antigen-presentation activities were totally abrogated by removal of class II MHC+ cells, but not by removal of CD11b+ cells or Ly6c+ cells, indicating that potent antigen-presenting cell activity was restricted to the class II MHC+ CD11b- Ly6c- subset (Langerhans cell-like/indeterminant cells). In conclusion, within a complex array of dermal leukocytes a murine dermal class II MHC+ cell population expressing a Langerhans cell-like/dendritic antigen-presenting cell phenotype and exhibiting potent antigen processing and presenting activity can be identified. The positioning of potent interstitial dendritic antigen-presenting cells at the interface of the vasculature with the dermal interstitium provides rapid access to an antigen-presenting cell as T cells first egress into the skin.

Animals↗
PubMed1993

Neutrophils, differentiated macrophages, and monocyte/macrophage antigen presenting cells infiltrate murine epidermis after UV injury.

We asked whether, as in humans, a population of antigen-presenting macrophages infiltrates the epidermis of ultraviolet (UV)-exposed BALB/c mice. Using three-color flow cytometry on cell suspensions plus in situ immunofluorescence microscopy, the phenotype of normal Langerhans cells was class II major histocompatibility complex (MHC+), CD11b+, NLDC-145+, BM8+ CD45+ and homogeneous. By contrast, in epidermal cells harvested 3 d following UV (UV-EC), there were two subsets of class II MHC+ cells: 1) class II MHChi CD11b+, and 2) class II MHClo CD11b-. Neither expressed the Langerhans cell markers BM8 and NLDC-145. In addition, there were two major populations of class II MHC- CD11b+ cells; half of these expressed the GR-1 neutrophil marker. Langerhans and dendritic epidermal T cells were markedly reduced after UV injury. By electron microscopy, immunomagnetic bead-purified CD11b+ cells in UV-EC were comprised of neutrophils, differentiated macrophages, and mononuclear cells with prominent lysosomes, but no Birbeck granules; the class II MHC+ subset resembled a monocytic cell in between differentiated macrophages and indeterminate dendritic cells. Functionally, immediately following in vivo UV exposure, the allogeneic antigen-presenting cell capacity of UV-EC was reduced to 21 +/- 6% of control epidermal cells (C-EC); by 3 d, antigen-presenting cell activity of UV-EC had recovered to 59 +/- 11% of C-EC, although at this time NLDC-145+ Langerhans cells had reached their lowest number. The recovered antigen-presenting cell activity was critically dependent upon the class II MHChiCD11b+ cells. Sensitization of BALB/c mice through skin that contained these antigen-presenting cells (3 d after UV) resulted in tolerance to dinitrofluorobenzene. By contrast, sensitization through UV-exposed skin immediately after the exposure resulted in unresponsiveness without tolerance, demonstrating temporal association of tolerance with leukocytic infiltration. In summary, murine epidermis responds to an acute UV injury in vivo with an initial abrogation of antigen-presenting activity followed by epidermal infiltration with neutrophils, differentiated macrophages, and monocytic antigen-presenting cells that are distinct from Langerhans cells with regard to expression of Langerhans cell markers and ultrastructure.

Animals↗
PubMed1986

Permeation of mouse skin and silicone rubber membranes by phenols: relationship to in vitro partitioning.

A discrepancy has been noted in the relationship between the relative skin permeabilities of phenols and their lipophilicities as expressed in commonly used octanol:water partition coefficients (PCoctanol:water). The lack of correlation between partitioning and permeability is seen with the nitrophenols, particularly 4-nitrophenol. In the present study, the permeability coefficients-of 4-nitrophenol and several other phenols through skin and a model lipophilic membrane made of silicone rubber were found to be independent of concentration, ruling out concentration-dependent molecular aggregation as the cause of the partitioning-permeability incongruity. An unexpectedly low permeation rate was observed for the diffusion of 4-nitrophenol through the synthetic, silicone rubber membrane, confirming the anomalous position of this phenol in permeability relative to the octanol:water partitioning scale. However, when oil:water (o/w) partition coefficients for the phenolic compounds based on either n-hexane, CH2Cl2, CHCl3, or silicone rubber as the water immiscible phase are used, permeability coefficients for the skin and the synthetic membrane followed expected permeation-partitioning dependencies. On this basis, it appears that PCoctanol:water does not properly reflect the lipophilicity of the phenols with respect to partitioning into skin and silicone rubber during mass transfer.

Animals↗