Leukotriene D4 upregulates eosinophil adhesion via the cysteinyl leukotriene 1 receptor.
BACKGROUND
Eosinophils (EOS) are one of the cellular sources of cysteinyl leukotrienes (cysLTs) in allergic inflammation. There is evidence that cysLT(1)receptor antagonists possess anti-inflammatory properties in vivo in asthmatic airways. Although the exact mechanism of action remains unknown, cysLTs might regulate the cellular responses involved in allergic inflammation.


OBJECTIVE
The present study was undertaken to examine whether LTD(4)modifies the adhesive property of EOS.


METHODS
EOS were isolated from the blood of healthy subjects. Their adhesion to tissue culture plates or recombinant human (rh) adhesion proteins was then examined in the presence or absence of LTD(4).


RESULTS
LTD(4)significantly augmented EOS adhesion to tissue culture plates (adhesion: 5.0% +/- 0.5% by medium control vs 9.1% +/- 1.2% by 1 micromol/L; P <.01; n = 10). The enhanced adhesion induced by LTD(4) was blocked by pranlukast, a cysLT(1) receptor antagonist, or an anti-beta(2) integrin antibody. Flow cytometry analysis revealed that LTD(4) significantly enhanced the expression of CD11b and CD18 on the EOS surface. Finally, LTD(4) augmented EOS adhesion to rh intercellular cell adhesion molecule 1 but not to rh vascular cell adhesion molecule 1 or fibronectin.


CONCLUSIONS
The results suggest that LTD(4) directly upregulates the adhesive property of EOS via the cysLT(1) receptor and beta(2) integrin. LTD(4) generated from EOS or cells of some other type might contribute to the development of phenotypic change in airway EOS.
Nagata
Makoto
M
Pulmonary Division, Second Department of Internal Medicine, Saitama Medical School.
Saito
Keiko
K
Tsuchiya
Koji
K
Sakamoto
Yoshio
Y
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D018821:CD18 Antigens / Q000032:analysis / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D017998:Leukotriene D4 / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000032:analysis; D008565:Membrane Proteins; D018077:Receptors, Leukotriene / Q000502:physiology*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D018799:Intercellular Adhesion Molecule-1; D017998:Leukotriene D4; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor