Pentamidine isethionate reduces Ia expression and antigen presentation by Langerhans cells and inhibits the contact hypersensitivity reaction. 1991

B L Blaylock, and Y Kouchi, and C E Comment, and E Corsini, and G J Rosenthal, and M I Luster
Immunotoxicology Group, National Institute of Environment Health Sciences, Research Triangle Park, NC 27709.

The mechanism of action of pentamidine isethionate, a diamidino compound used in the treatment of Pneumocystis carinii pneumonia, is unknown. We recently reported that this drug may inhibit the release of inflammatory mediators from alveolar macrophages, which may be associated with its antiparasite activity. As a potential anti-inflammatory agent, we report that topically applied pentamidine reduces ear swelling in the contact hypersensitivity reaction to oxazolone in B6C3F1 mice. The application of pentamidine must occur within 1 h, at the challenge site, to be effective. Topical application appears necessary, because i.v. injection had no effect on reduction of ear swelling. In dose-response studies, a 50% reduction in ear swelling was achieved with as little as 20 micrograms of pentamidine. Pentamidine did not affect Ag transport from the challenge site to the draining lymph nodes, as measured by FITC transport. However, there was a 30 to 40% reduction in epidermal cells expressing Ia Ag from pentamidine-treated mouse ears, compared with control. Ia expression is almost exclusively limited to Langerhans cells in the normal epidermis. This reduction in Ia expression was not due to simple depletion of Langerhans cells by pentamidine, because CD45 expression was unaffected. Concurrent with reduced Ia expression, Ag presentation by pentamidine-treated Langerhans cells was also reduced. Taken together, a mechanism of action for pentamidine in inhibition of the contact hypersensitivity reaction appears to be via a reduction in Ag presentation by decreasing Ia+ Langerhans cells.

UI MeSH Term Description Entries
D007801 Langerhans Cells Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS. Langerhans Cell,Dendritic Cells, Dermal,Dendritic Cells, Epidermal,Dendritic Cells, Skin,Dermal Dendritic Cells,Epidermal Dendritic Cells,Skin Dendritic Cells,Cell, Dermal Dendritic,Cell, Epidermal Dendritic,Cell, Langerhans,Cell, Skin Dendritic,Cells, Dermal Dendritic,Cells, Epidermal Dendritic,Cells, Langerhans,Cells, Skin Dendritic,Dendritic Cell, Dermal,Dendritic Cell, Epidermal,Dendritic Cell, Skin,Dermal Dendritic Cell,Epidermal Dendritic Cell,Skin Dendritic Cell
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D010081 Oxazolone Immunologic adjuvant and sensitizing agent. 2-Phenyl-4-(ethoxymethylene)oxazol-5-one,4-Ethoxymethylene-2-phenyloxazolone,4 Ethoxymethylene 2 phenyloxazolone
D010419 Pentamidine Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of PNEUMOCYSTIS pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. Pentamidine Isethionate,Diamidine,Lomidine,NebuPent,Pentacarinat,Pentam,Pentamidin,Pentamidine Mesylate
D003877 Dermatitis, Contact A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. Contact Dermatitis,Dermatitis Venenata,Eczema, Contact,Hypersensitivity, Contact,Sensitivity, Contact,Contact Dermatitides,Contact Eczema,Contact Hypersensitivities,Contact Hypersensitivity,Contact Sensitivities,Contact Sensitivity,Dermatitides, Contact,Hypersensitivities, Contact,Sensitivities, Contact
D005260 Female Females
D006649 Histocompatibility Antigens A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection. Transplantation Antigens,Antigens, Transplantation,Histocompatibility Antigen,LD Antigens,SD Antigens,Antigen, Histocompatibility,Antigens, Histocompatibility,Antigens, LD,Antigens, SD
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000938 Antigen-Presenting Cells A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors. Accessory Cells, Immunologic,Antigen-Presenting Cell,Immunologic Accessory Cells,Accessory Cell, Immunologic,Cell, Immunologic Accessory,Cells, Immunologic Accessory,Immunologic Accessory Cell,Antigen Presenting Cell,Antigen Presenting Cells,Cell, Antigen-Presenting,Cells, Antigen-Presenting
D000949 Histocompatibility Antigens Class II Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen. Antigens, Immune Response,Class II Antigens,Class II Histocompatibility Antigen,Class II Major Histocompatibility Antigen,Ia Antigens,Ia-Like Antigen,Ia-Like Antigens,Immune Response Antigens,Immune-Associated Antigens,Immune-Response-Associated Antigens,MHC Class II Molecule,MHC II Peptide,Class II Antigen,Class II Histocompatibility Antigens,Class II MHC Proteins,Class II Major Histocompatibility Antigens,Class II Major Histocompatibility Molecules,I-A Antigen,I-A-Antigen,IA Antigen,MHC Class II Molecules,MHC II Peptides,MHC-II Molecules,Antigen, Class II,Antigen, I-A,Antigen, IA,Antigen, Ia-Like,Antigens, Class II,Antigens, Ia,Antigens, Ia-Like,Antigens, Immune-Associated,Antigens, Immune-Response-Associated,I A Antigen,II Peptide, MHC,Ia Like Antigen,Ia Like Antigens,Immune Associated Antigens,Immune Response Associated Antigens,MHC II Molecules,Molecules, MHC-II,Peptide, MHC II,Peptides, MHC II

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