Cetirizine and levocetirizine inhibit eotaxin-induced eosinophil transendothelial migration through human dermal or lung microvascular endothelial cells

Lynn Marie Thomson, Morgan Graeme Blaylock, Darren William Sexton, A. Campbell, Garry Michael Walsh

Research output: Contribution to journalArticle

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Abstract

Background Several second-generation antihistamines have documented anti-inflammatory effects which appear independent of H-1-receptor blockade. We investigated the inhibitory effect of cetirizine and its active enantiomer levocetirizine on eosinophil transendothelial migration (TEM) through monolayers of normal human dermal microvascular endothelial cells (HMVEC-d) or human lung microvascular endothelial cells (HMVEC-l).

Methods HMVEC-d or HMVEC-l were grown to confluence on micropore filters in transwells inserted into a 24-well tissue culture dish. Eosinophils were isolated by density gradient centrifugation and negative immunomagnetic selection. Untreated eosinophils or eosinophils pre-incubated (30 min at 37 degreesC) with a concentration range of cetirizine or levocetirizine (10(-5) to 10 (-9) m) were added to the upper chamber of the transwell which was incubated for 60 min at 37 degreesC. Both spontaneous eosinophil TEM and TEM to 100 ng/mL of human eotaxin in the lower chamber were assessed.

Results Between 8 and 10% of the eosinophils added to the upper chamber underwent spontaneous TEM through HMVEC-d or HMVEC-l. The addition of eotaxin to the lower chamber enhanced eosinophil TEM through HMVEC-d or HMVEC-l monolayers to over 20%, i.e. an enhanced TEM of approximately 100% in each case. Pre-incubation of eosinophils with cetirizine or levocetirizine dose-dependently inhibited eosinophil TEM to eotaxin through both HMVEC-d or HMVEC-l with total inhibition of eotaxin-induced TEM observed at 10(-8) m for HMVEC-d and 10(-7) m for HMVEC-l. Both drugs gave a reduced but significant inhibition of eosinophil TEM at lower concentrations. No concentration of cetirizine or levocetirizine had any significant effect on expression of CD11b, CD18 or CD49d by either resting or eotaxin-stimulated eosinophils. Furthermore, no effect on spontaneous eosinophil TEM, or eosinophil viability was seen with any concentration of cetirizine or levocetirizine.

Conclusion Levocetirizine inhibits eotaxin-induced eosinophil TEM through both dermal and lung microvascular endothelial cells suggesting that, like cetirizine, levocetirizine has potential anti-inflammatory effects.

Original languageEnglish
Pages (from-to)1187-1192
Number of pages5
JournalClinical & experimental allergy
Volume32
Issue number8
DOIs
Publication statusPublished - Aug 2002

Keywords

  • cetirizine
  • eosinophil
  • eotaxin
  • levocetirizine
  • transendothelial migration
  • HEALTHY ADULT VOLUNTEERS
  • ADHESION MOLECULES
  • PAF-ACETHER
  • ANTIHISTAMINES
  • HISTAMINE
  • RELEASE
  • RECRUITMENT
  • MODULATION
  • APOPTOSIS
  • SKIN

Cite this

Cetirizine and levocetirizine inhibit eotaxin-induced eosinophil transendothelial migration through human dermal or lung microvascular endothelial cells. / Thomson, Lynn Marie; Blaylock, Morgan Graeme; Sexton, Darren William; Campbell, A.; Walsh, Garry Michael.

In: Clinical & experimental allergy, Vol. 32, No. 8, 08.2002, p. 1187-1192.

Research output: Contribution to journalArticle

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title = "Cetirizine and levocetirizine inhibit eotaxin-induced eosinophil transendothelial migration through human dermal or lung microvascular endothelial cells",
abstract = "Background Several second-generation antihistamines have documented anti-inflammatory effects which appear independent of H-1-receptor blockade. We investigated the inhibitory effect of cetirizine and its active enantiomer levocetirizine on eosinophil transendothelial migration (TEM) through monolayers of normal human dermal microvascular endothelial cells (HMVEC-d) or human lung microvascular endothelial cells (HMVEC-l).Methods HMVEC-d or HMVEC-l were grown to confluence on micropore filters in transwells inserted into a 24-well tissue culture dish. Eosinophils were isolated by density gradient centrifugation and negative immunomagnetic selection. Untreated eosinophils or eosinophils pre-incubated (30 min at 37 degreesC) with a concentration range of cetirizine or levocetirizine (10(-5) to 10 (-9) m) were added to the upper chamber of the transwell which was incubated for 60 min at 37 degreesC. Both spontaneous eosinophil TEM and TEM to 100 ng/mL of human eotaxin in the lower chamber were assessed.Results Between 8 and 10{\%} of the eosinophils added to the upper chamber underwent spontaneous TEM through HMVEC-d or HMVEC-l. The addition of eotaxin to the lower chamber enhanced eosinophil TEM through HMVEC-d or HMVEC-l monolayers to over 20{\%}, i.e. an enhanced TEM of approximately 100{\%} in each case. Pre-incubation of eosinophils with cetirizine or levocetirizine dose-dependently inhibited eosinophil TEM to eotaxin through both HMVEC-d or HMVEC-l with total inhibition of eotaxin-induced TEM observed at 10(-8) m for HMVEC-d and 10(-7) m for HMVEC-l. Both drugs gave a reduced but significant inhibition of eosinophil TEM at lower concentrations. No concentration of cetirizine or levocetirizine had any significant effect on expression of CD11b, CD18 or CD49d by either resting or eotaxin-stimulated eosinophils. Furthermore, no effect on spontaneous eosinophil TEM, or eosinophil viability was seen with any concentration of cetirizine or levocetirizine.Conclusion Levocetirizine inhibits eotaxin-induced eosinophil TEM through both dermal and lung microvascular endothelial cells suggesting that, like cetirizine, levocetirizine has potential anti-inflammatory effects.",
keywords = "cetirizine, eosinophil, eotaxin, levocetirizine, transendothelial migration, HEALTHY ADULT VOLUNTEERS, ADHESION MOLECULES, PAF-ACETHER, ANTIHISTAMINES, HISTAMINE, RELEASE, RECRUITMENT, MODULATION, APOPTOSIS, SKIN",
author = "Thomson, {Lynn Marie} and Blaylock, {Morgan Graeme} and Sexton, {Darren William} and A. Campbell and Walsh, {Garry Michael}",
year = "2002",
month = "8",
doi = "10.1046/J.1365-2745.2002.01444.X",
language = "English",
volume = "32",
pages = "1187--1192",
journal = "Clinical & experimental allergy",
issn = "0954-7894",
publisher = "Wiley-Blackwell",
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TY - JOUR

T1 - Cetirizine and levocetirizine inhibit eotaxin-induced eosinophil transendothelial migration through human dermal or lung microvascular endothelial cells

AU - Thomson, Lynn Marie

AU - Blaylock, Morgan Graeme

AU - Sexton, Darren William

AU - Campbell, A.

AU - Walsh, Garry Michael

PY - 2002/8

Y1 - 2002/8

N2 - Background Several second-generation antihistamines have documented anti-inflammatory effects which appear independent of H-1-receptor blockade. We investigated the inhibitory effect of cetirizine and its active enantiomer levocetirizine on eosinophil transendothelial migration (TEM) through monolayers of normal human dermal microvascular endothelial cells (HMVEC-d) or human lung microvascular endothelial cells (HMVEC-l).Methods HMVEC-d or HMVEC-l were grown to confluence on micropore filters in transwells inserted into a 24-well tissue culture dish. Eosinophils were isolated by density gradient centrifugation and negative immunomagnetic selection. Untreated eosinophils or eosinophils pre-incubated (30 min at 37 degreesC) with a concentration range of cetirizine or levocetirizine (10(-5) to 10 (-9) m) were added to the upper chamber of the transwell which was incubated for 60 min at 37 degreesC. Both spontaneous eosinophil TEM and TEM to 100 ng/mL of human eotaxin in the lower chamber were assessed.Results Between 8 and 10% of the eosinophils added to the upper chamber underwent spontaneous TEM through HMVEC-d or HMVEC-l. The addition of eotaxin to the lower chamber enhanced eosinophil TEM through HMVEC-d or HMVEC-l monolayers to over 20%, i.e. an enhanced TEM of approximately 100% in each case. Pre-incubation of eosinophils with cetirizine or levocetirizine dose-dependently inhibited eosinophil TEM to eotaxin through both HMVEC-d or HMVEC-l with total inhibition of eotaxin-induced TEM observed at 10(-8) m for HMVEC-d and 10(-7) m for HMVEC-l. Both drugs gave a reduced but significant inhibition of eosinophil TEM at lower concentrations. No concentration of cetirizine or levocetirizine had any significant effect on expression of CD11b, CD18 or CD49d by either resting or eotaxin-stimulated eosinophils. Furthermore, no effect on spontaneous eosinophil TEM, or eosinophil viability was seen with any concentration of cetirizine or levocetirizine.Conclusion Levocetirizine inhibits eotaxin-induced eosinophil TEM through both dermal and lung microvascular endothelial cells suggesting that, like cetirizine, levocetirizine has potential anti-inflammatory effects.

AB - Background Several second-generation antihistamines have documented anti-inflammatory effects which appear independent of H-1-receptor blockade. We investigated the inhibitory effect of cetirizine and its active enantiomer levocetirizine on eosinophil transendothelial migration (TEM) through monolayers of normal human dermal microvascular endothelial cells (HMVEC-d) or human lung microvascular endothelial cells (HMVEC-l).Methods HMVEC-d or HMVEC-l were grown to confluence on micropore filters in transwells inserted into a 24-well tissue culture dish. Eosinophils were isolated by density gradient centrifugation and negative immunomagnetic selection. Untreated eosinophils or eosinophils pre-incubated (30 min at 37 degreesC) with a concentration range of cetirizine or levocetirizine (10(-5) to 10 (-9) m) were added to the upper chamber of the transwell which was incubated for 60 min at 37 degreesC. Both spontaneous eosinophil TEM and TEM to 100 ng/mL of human eotaxin in the lower chamber were assessed.Results Between 8 and 10% of the eosinophils added to the upper chamber underwent spontaneous TEM through HMVEC-d or HMVEC-l. The addition of eotaxin to the lower chamber enhanced eosinophil TEM through HMVEC-d or HMVEC-l monolayers to over 20%, i.e. an enhanced TEM of approximately 100% in each case. Pre-incubation of eosinophils with cetirizine or levocetirizine dose-dependently inhibited eosinophil TEM to eotaxin through both HMVEC-d or HMVEC-l with total inhibition of eotaxin-induced TEM observed at 10(-8) m for HMVEC-d and 10(-7) m for HMVEC-l. Both drugs gave a reduced but significant inhibition of eosinophil TEM at lower concentrations. No concentration of cetirizine or levocetirizine had any significant effect on expression of CD11b, CD18 or CD49d by either resting or eotaxin-stimulated eosinophils. Furthermore, no effect on spontaneous eosinophil TEM, or eosinophil viability was seen with any concentration of cetirizine or levocetirizine.Conclusion Levocetirizine inhibits eotaxin-induced eosinophil TEM through both dermal and lung microvascular endothelial cells suggesting that, like cetirizine, levocetirizine has potential anti-inflammatory effects.

KW - cetirizine

KW - eosinophil

KW - eotaxin

KW - levocetirizine

KW - transendothelial migration

KW - HEALTHY ADULT VOLUNTEERS

KW - ADHESION MOLECULES

KW - PAF-ACETHER

KW - ANTIHISTAMINES

KW - HISTAMINE

KW - RELEASE

KW - RECRUITMENT

KW - MODULATION

KW - APOPTOSIS

KW - SKIN

U2 - 10.1046/J.1365-2745.2002.01444.X

DO - 10.1046/J.1365-2745.2002.01444.X

M3 - Article

VL - 32

SP - 1187

EP - 1192

JO - Clinical & experimental allergy

JF - Clinical & experimental allergy

SN - 0954-7894

IS - 8

ER -