Adhesion of peripheral blood mononuclear cells and CD4+ T cells from patients with psoriasis to cultured endothelial cells via the interaction between lymphocyte function-associated antigen type 1 and intercellular adhesion molecule 1.
BACKGROUND
The adhesion of CD4+ T cells to endothelial cells and their subsequent migration to skin tissue are essential to develop the psoriatic skin lesion. However, few studies have examined the role of adhesion molecules in the binding of T cells from patients with chronic plaque psoriasis to endothelial cells in vitro; thus, the adhesion molecules responsible for the development of skin lesions are still unclear.


OBJECTIVE
To identify the responsible adhesion molecules in the interaction between CD4+ T cells in patients with chronic plaque psoriasis and cytokine-stimulated endothelial cells.


METHODS
An in vitro adhesion assay between Calcein-labelled peripheral blood mononuclear cells (PBMC) and cytokine-stimulated human endothelial cultures, which exhibit a higher adhesion capacity to PBMC, was established, and the adhesion-inhibitory effects of a panel of antiadhesion molecule antibodies on the adhesion of PBMC from patients with psoriasis to endothelial cells were examined. Then, the inhibitory effects of selected antibodies acting on the interaction between CD4+ T cells from patients with psoriasis (purified by negative magnetic cell sorting) and cultured endothelial cells were examined.


RESULTS
A significant increase (P < 0.01) in the adhesion of psoriatic PBMC to both endothelial cultures, human skin microvascular endothelial cells from adults (HMVEC-Ad) and human coronary arterial endothelial cells (HCAEC), compared with healthy PBMC, was demonstrated in our in vitro cell adhesion assay. Pretreatment of both endothelial cultures with tumour necrosis factor (TNF)-alpha (1000 U mL(-1)) induced the most frequent adhesion of PBMC from patients with psoriasis among the three inflammatory cytokines examined, i.e. TNF-alpha, interleukin-1beta and interferon-gamma [TNF-alpha-treated vs. nontreated: P < 0.001 (in both HMVEC-Ad and HCAEC)]. In both endothelial cultures treated with TNF-alpha, PBMC from patients with psoriasis exhibited significantly more frequent adhesion compared with those from healthy individuals (P < 0.001). The TNF-alpha-stimulated HMVEC-Ad, which exhibited the most frequent adhesion of PBMC, were selected for adhesion-inhibition experiments using monoclonal antibodies (mAbs) to adhesion molecules that are upregulated in psoriatic lesions, and the combination of antilymphocyte function-associated antigen type 1 (LFA-1) and anti-intercellular adhesion molecule 1 (ICAM-1) mAbs gave the greatest reduction of adhesion of PBMC from patients with psoriasis (approximately 69% reduction; P < 0.01). This combination of mAbs significantly reduced also the adhesion of CD4+ T cells from patients with psoriasis to TNF-alpha-stimulated HMVEC-Ad (approximately 62% reduction), compared with pretreatment with isotype control mAbs (P < 0.01).


CONCLUSIONS
These findings indicate that the LFA-1/ICAM-1 interaction plays a major role in the adhesion of CD4+ T cells to endothelial cells and that TNF-alpha might play an important role for the induction of adhesion molecules on endothelial cells at psoriatic skin lesions.
Watabe
D
D
Department of Pathology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka 020-8505, Japan.
Kanno
H
H
Yoshida
A
A
Kurose
A
A
Akasaka
T
T
Sawai
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000276:immunology; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology*; D012867:Skin / Q000098:blood supply; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1