Involvement of L-Selectin in Contact Hypersensitivity Responses Augmented by Auditory Stress

Abstract

Stress affects the pathophysiology of cutaneous immune reactions, including contact hypersensitivity (CH) in individuals sensitized with sensitizing hapten, where local endothelial cell activation plays a critical role. To clarify the effects of stress in cutaneous immune reactions, we selected a CH model using annoying sound as a stress. Furthermore, we conducted the stress experiments by using selectin-deficient mice to determine the involvement of selectin molecules regarding local endothelial activation. Auditory stress augmented CH responses in the present study. Namely, ear thickness and mast cell numbers were significantly increased in stressed CH mice. mRNA expression of preprotachykinin-A, a precursor of substance-P; interferon-gamma; interleukin (IL)-4; IL-6; and tumor necrosis factor-alpha significantly increased in stressed CH mice. Furthermore, stressed L-selectin-deficient mice showed significant decreases in all parameters mentioned above relative to stressed wild-type mice in CH response. Meanwhile, treatment with anti-L-selectin Ab resulted in a significant decrease in ear thickness and mRNA levels of interferon-gamma, IL-4, IL-6, and tumor necrosis factor-alpha, but failed to significantly reduce preprotachykinin-A mRNA levels and mast cell numbers. Our results indicated that auditory stress enhances CH response and that the augmentation of this CH response might be mediated through L-selectin, but not through P- or E-selectin pathways.

Substance P Is a Key Mediator of Stress-Induced Protection from Allergic Sensitization via Modified Antigen Presentation

“…In these experiments, SP activation of DC during the effector phase of a Th1-driven inflammation triggered a massive and rapid LC mobilization out of the epidermis and enhanced inflammation. An inflammation-promoting effect of SP signaling was also demonstrated in other Th1 and neurogenic inflammation-dominated neuroimmune constellations, such as during the elicitation of contact hypersensitivity (7,58,59), during provocation of AlD (32)(33)(34), in hair loss (60), and in healthy murine skin and lymphocytes (34,39,40). This effect appears to be further facilitated by stress-and nerve growth factor-induced plasticity of the peripheral nervous system and malfunctioning HPA responsiveness (32,34,39,61,62).…”

“…In allergic disorders-especially in people with an atopic predisposition-the net effect of the stress response was generally reported to contribute to acute exacerbation and even onset of disease (2)(3)(4)(5)(6)(7). The key mechanisms involved are altered immune competence and neuronal plasticity after stress experience as a result of an HPA-and SA-generated Th2 bias on the one hand and local proinflammatory NNA activation on the other hand (8)(9)(10).…”

Stress-induced redistribution of immune cells—From barracks to boulevards to battlefields: A tale of three hormones – Curt Richter Award Winner

“…While a review of these studies is beyond the scope of this manuscript, taken together, they suggest that changes in leukocyte adhesion molecule conformation/expression may mediate aspects of both the mobilization and trafficking effects of stress and stress hormones. In support of a role for CD62L in mediating the immuno-enhancing effects of short-term stress, a recent study has shown that the acute stress-induced enhancement of skin cell-mediated immunity is significantly decreased in CD62L deficient mice (Bae et al, 2011). Other studies have suggested that glucocorticoid hormones suppress neutrophil CD62L mRNA expression and that this induces a decrease in cell-surface protein expression of CD62L that is correlated with a glucocorticoid-induced neutrophilia (Weber et al, 2001).…”