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Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
Keratinocytes resident in normal human skin constitutively express, at low levels, the intercellular adhesion
A Lonati1, M A Mommaas, G Pasolini
1Department of Dermatology, Spedali Civili, Brescia, Italy.
Insights
Intercellular adhesion molecule-1 (ICAM-1) is expressed at low levels on normal skin keratinocytes (KC). This limited ICAM-1 expression on KC may prevent unwanted immune cell interactions in resting skin.
Area of Science:
- Dermatology
- Immunology
- Cell Biology
Background:
- Intercellular adhesion molecule-1 (ICAM-1) expression is known on keratinocytes (KC) in inflammatory skin conditions.
- KC in normal skin typically show minimal ICAM-1 expression using standard immunocytochemistry.
- Epithelial cells in other organs constitutively express ICAM-1, though weakly.
Purpose of the Study:
- To investigate the constitutive expression of ICAM-1 on resting keratinocytes (KC) in normal skin.
- To utilize a highly sensitive in situ immunogold labeling technique for detecting low-level ICAM-1 expression.
- To understand the role of ICAM-1 in normal epidermal immune cell trafficking.
Main Methods:
- In situ immunogold labeling of ultracryosections for ICAM-1 detection.
- Semiquantitative analysis of gold particle density on KC cell membranes.
- Examination of 500 resident KC in normal human skin ultracryosections.
Main Results:
- A small percentage (14.6%) of resident KC exhibited ICAM-1 expression on their cell membranes.
- The density of ICAM-1 gold particles was low (13.72 +/- 4.6 per KC section).
- This expression was statistically significant compared to controls (P < 0.005).
Conclusions:
- Resting keratinocytes in normal skin exhibit a low but significant constitutive expression of ICAM-1.
- This limited ICAM-1 expression may regulate the movement of Langerhans cells and leukocytes into the epidermis.
- Restricted ICAM-1 on KC likely prevents inappropriate interactions with immune cells in a non-inflamed state.
Abstract:
The expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes (KC) was previously demonstrated in biopsies from various inflammatory skin lesions. KC were, however, found virtually ICAM-1 negative, in normal skin, when the same immunocytochemical techniques were employed. By contrast, epithelial cells resident in different organs constitutively express ICAM-1, albeit weakly. The aim of the present study was to use an immunostaining system more sensitive than the conventional immunocytochemistry, namely the in situ immunogold labelling of ultracryosections, to investigate the constitutive ICAM-1 expression by resting KC in normal skin, in vivo. The semiquantitative analysis performed on 500 resident KC, visualized within tissue ultracryosections of normal human skin, revealed that gold granules were present long the cell membrane in a small percentage (14.6%) of resident KC. The density of gold particles (10 nm sized) observed on the cell surface per KC section was as scarce as 13.72 +/- 4.6 (mean +/- standard deviation), although highly significant when compared with controls (P < 0.005). This indicates the presumably low expression of ICAM-1 moieties on the plasma membrane of this KC subset. This ICAM-1 expression could be important in modulating the trafficking to and from normal epidermis of migrating Langerhans cells and occasional leucocytes. The fact that the ICAM-1 expression on KC in normal skin is limited can be considered favourable, because it can account for the prevention of inappropriate KC/leucocyte interactions in the resting cutaneous environment.
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