Functional changes of dendritic cells in hypersensitivity reactions to amoxicillin

C. M F Lima, John Thomas Schroeder, C. E S Galvão, F. M. Castro, J. Kalil, N Franklin Adkinson

Research output: Contribution to journalArticle

Abstract

A better understanding of dendritic cell (DC) involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC) and myeloid DC (mDC). β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6) production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC) suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.

Original languageEnglish (US)
Pages (from-to)964-968
Number of pages5
JournalBrazilian Journal of Medical and Biological Research
Volume43
Issue number10
DOIs
StatePublished - Oct 2010

Fingerprint

Amoxicillin
Dendritic Cells
Hypersensitivity
Allergies
Drug Hypersensitivity
Pharmaceutical Preparations
Penicillins
Interleukin-6
Basophils
Suspensions
Lactams
Cell Separation
Haptens
Gravitation
Myeloid Cells
Exanthema
Allergens
Blood Cells
Blood
Chemical activation

Keywords

  • β-lactam hypersensitivity
  • Dendritic cells
  • Drug allergy
  • Plasmacytoid dendritic cells

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Physiology
  • Biochemistry
  • Biophysics
  • Cell Biology

Cite this

Functional changes of dendritic cells in hypersensitivity reactions to amoxicillin. / Lima, C. M F; Schroeder, John Thomas; Galvão, C. E S; Castro, F. M.; Kalil, J.; Adkinson, N Franklin.

In: Brazilian Journal of Medical and Biological Research, Vol. 43, No. 10, 10.2010, p. 964-968.

Research output: Contribution to journalArticle

@article{32b86f7336754d6db0f83bd554d18806,
title = "Functional changes of dendritic cells in hypersensitivity reactions to amoxicillin",
abstract = "A better understanding of dendritic cell (DC) involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC) and myeloid DC (mDC). β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6) production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC) suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.",
keywords = "β-lactam hypersensitivity, Dendritic cells, Drug allergy, Plasmacytoid dendritic cells",
author = "Lima, {C. M F} and Schroeder, {John Thomas} and Galv{\~a}o, {C. E S} and Castro, {F. M.} and J. Kalil and Adkinson, {N Franklin}",
year = "2010",
month = "10",
doi = "10.1590/S0100-879X2010007500096",
language = "English (US)",
volume = "43",
pages = "964--968",
journal = "Brazilian Journal of Medical and Biological Research",
issn = "0100-879X",
publisher = "Associacao Brasileira de Divulgacao Cientifica",
number = "10",

}

TY - JOUR

T1 - Functional changes of dendritic cells in hypersensitivity reactions to amoxicillin

AU - Lima, C. M F

AU - Schroeder, John Thomas

AU - Galvão, C. E S

AU - Castro, F. M.

AU - Kalil, J.

AU - Adkinson, N Franklin

PY - 2010/10

Y1 - 2010/10

N2 - A better understanding of dendritic cell (DC) involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC) and myeloid DC (mDC). β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6) production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC) suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.

AB - A better understanding of dendritic cell (DC) involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC) and myeloid DC (mDC). β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6) production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC) suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.

KW - β-lactam hypersensitivity

KW - Dendritic cells

KW - Drug allergy

KW - Plasmacytoid dendritic cells

UR - http://www.scopus.com/inward/record.url?scp=78149275080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149275080&partnerID=8YFLogxK

U2 - 10.1590/S0100-879X2010007500096

DO - 10.1590/S0100-879X2010007500096

M3 - Article

C2 - 20878012

AN - SCOPUS:78149275080

VL - 43

SP - 964

EP - 968

JO - Brazilian Journal of Medical and Biological Research

JF - Brazilian Journal of Medical and Biological Research

SN - 0100-879X

IS - 10

ER -