Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic cells.

Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic cells. Research Abstract Details 

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Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic cells. Abstract Text:

Sanjoy Roychowdhury,Piyush M Vyas,Craig K Svensson,

Bioactivation of sulfonamides and the subsequent formation of haptenated proteins is believed to be a critical step in the development of hypersensitivity reactions to these drugs. Numerous lines of evidence suggest that the presence of such adducts in dendritic cells (DCs) migrating to draining lymph nodes is essential for the development of cutaneous reactions to xenobiotics. Our objective was to determine the ability of human DCs to form drug-protein covalent adducts when exposed to sulfamethoxazole (SMX), dapsone (DDS), or their arylhydroxylamine metabolites [sulfamethoxazole hydroxylamine (S-NOH) and dapsone hydroxylamine (D-NOH)] and to take up preformed adduct. Naive and immature CD34+ KG-1 cells were incubated with SMX, DDS, or metabolites. Formation of haptenated proteins was probed using confocal microscopy and ELISA. Cells were also incubated with preformed adduct (drug-bovine serum albumin conjugate), and uptake was determined using confocal microscopy. Both naive and immature KG-1 cells were able to bioactivate DDS, forming drug-protein adducts, whereas cells showed very little protein haptenation when exposed to SMX. Exposure to S-NOH or D-NOH resulted in protein haptenation in both cell types. Both immature and naive KG-1 cells were able to take up preformed haptenated proteins. Thus, DCs may acquire haptenated proteins associated with drugs via intracellular bioactivation, uptake of reactive metabolites, or uptake of adduct formed and released by adjacent cells (e.g., keratinocytes).

Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic cells. Publishing Authors By Initials

S Roychowdhury,PM Vyas,CK Svensson,

For similar natural sciences: time: time factors research abstracts see: natural sciences: time: time factors research

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Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Drug metabolism and disposition: the biological fa

VOLUME: 35

Page Numbers: 676-81

Journal Abbreviation: Drug Metab. Dispos.

ISSN: 0090-9556

DAY: 12

MONTH: 01

YEAR: 2007

Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9421550

Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic cells. Keywords Mesh Terms:

KEYWORDS: Time Factors

MESH TERMS: metabolism

Chemical & Substance for Abstract: Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic cells. Information

Substance Name: dimethylaniline monooxygenase (N-oxide f

Registry Number: EC 1.14.13.8

Grant and Affiliation Information for Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic cells.

AFFILIATION: Office of the Dean, College of Pharmacy, Nursing and Health Sciences, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 49707, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM63821

ACRONYM: GM

MEDLINETA: Drug Metab Dispos

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