Atopic dermatitis (AD) is a chronic inflammatory skin disease with specific immune and inflammatory mechanisms. Atopy is among the major features of the diagnosis criteria for AD but is not an essential feature. Thus, patients diagnosed with AD can be atopic or non-atopic. This review focuses on the role of IgE, mast cells, and eosinophils in the pathogenesis of AD. The known functions of IgE in allergic inflammation suggest that IgE and IgE-mediated mast cell and eosinophil activation contribute to AD, but direct evidence supporting this is scarce. The level of IgE (thus the degree of allergic sensitization) is associated with severity of AD and contributed by abnormality of skin barrier, a key feature of AD. The function of IgE in development of AD is supported by the beneficial effect of anti-IgE therapy in a number of clinical studies. The role of mast cells in AD is suggested by the increase in the mast cell number and mast cell activation in AD lesions and the association between mast cell activation and AD. It is further suggested by their role in mouse models of AD as well as by the effect of therapeutic agents for AD that can affect mast cells. The role of eosinophils in AD is suggested by the presence of eosinophilia in AD patients and eosinophil infiltrates in AD lesions. It is further supported by information that links AD to cytokines and chemokines associated with production, recruitment, and activation of eosinophils.

We report herein the establishment of a single-cell compression method based on force measurements in atomic force microscopy (AFM). The high-resolution bright-field or confocal laser scanning microscopy guides the location of the AFM probe and then monitors the deformation of cell shape, while microsphere-modified AFM probes compress the cell and measure the force. Force and deformation profiles of living cells reveal a cubic relationship at small deformation (<30%), multiple peaks at 30-70% compression, and a rapid increase at over 80% deformation. The initial compression may be described qualitatively and quantitatively using a simple model of a nonpermeable balloon filled with incompressible fluid. Stress peaks reflect cell membrane rupture, followed by the deformation and rupture of intracellular components, beyond which the cell responses become irreversible. The Young's modulus and bending constant of living cell membranes are extracted from the balloon models, with 10-30 MPa and 17-52 kT, respectively. The initial compression of dead and fixed cells is modeled using Hertzian contact theory, assuming that the cell is a homogeneous sphere. Dead cells exhibit a cytoskeleton elasticity of 4-7.5 kPa, while fixation treatment leads to a dramatic increase in the cytoskeletal Young's modulus (150-230 kPa) due to protein cross-linking by imine bonds. These results demonstrate the high sensitivity of the single-cell compression method to the molecular-level structural changes of cells, which suggests a new generic platform for investigating cell mechanics in tissue engineering and cancer research.

Galectin-3 is a member of a ␤-galactoside-binding animal lectin family. Previous in vitro studies have demonstrated that galectin-3 is involved in a number of activities; however, the roles of this lectin in physiological and pathological processes in vivo remain to be elucidated. Herein, we show, in a murine model of ovalbumin (OVA)-induced asthma that 1) peribronchial inflammatory cells expressed large amounts of galectin-3; 2) bronchoalveolar lavage fluid from OVAchallenged mice contained significantly higher levels of galectin-3 compared to control mice; and 3) macrophages in bronchoalveolar lavage fluid were the major cell type that contained galectin-3. We investigated the role of galectin-3 in the allergic airway response by comparing galectin-3-deficient (gal3 ؊/؊ ) mice and wild-type (gal3 ؉/؉ ) mice. OVA-sensitized gal3 ؊/؊ mice developed fewer eosinophils and lower goblet cell metaplasia, after airway OVA challenge compared to similarly treated gal3 ؉/؉ mice. In addition, the OVA-sensitized gal3 ؊/؊ mice developed significantly less airway hyperresponsiveness after airway OVA challenge compared to gal3 ؉/؉ mice. Finally, gal3 ؊/؊ mice developed a lower Th2 response, but a higher Th1 response, suggesting that galectin-3 regulates the Th1/Th2 response. We conclude that galectin-3 may play an important role in the pathogenesis of asthma and inhibitors of this lectin may prove useful for treatment of this disease.

Galectin-3 is absent in resting CD4+ and CD8+ T cells but is inducible by various stimuli. These include viral transactivating factors, T-cell receptor (TCR) ligation, and calcium ionophores. In addition, galectin-3 is constitutively expressed in human regulatory T cells and CD4+ memory T cells. Galectin-3 exerts extracellular functions because of its lectin activity and recognition of cell surface and extracellular matrix glycans. These include cell activation, adhesion, induction of apoptosis, and formation of lattices with cell surface glycoprotein receptors. Formation of lattices can result in restriction of receptor mobility and cause attenuation of receptor functions. Consistent with the presence of galectin-3 in intracellular locations, several functions have been described for this protein inside T cells. These include inhibition of apoptosis, promotion of cell growth, and regulation of TCR signal transduction. Studies of cell surface glycosylation have led to convergence of glycobiology and galectin biology and provided new clues on how galectin-3 may participate in the regulation of cell surface receptor activities. The rapid expansion of the field of galectin research has positioned galectin-3 as a key regulator in T-cell functions.

Galectin-12 is a member of the galectin family consisting of ␤-galactoside-binding proteins with conserved carbohydrate recognition domains. This protein is preferentially expressed in peripheral blood leukocytes and adipocytes. We previously showed that galectin-12 is induced by cell cycle block at the G 1 phase and causes