ovalbumin and Wounds-and-Injuries

Allergen sources such as mites, insects, fungi, and pollen contain proteases. Airway exposure to proteases induces allergic airway inflammation and IgE/IgG1 responses via IL-33-dependent mechanisms in mice. We examined the epicutaneous sensitization of mice to a model protease allergen, papain; the effects of tape stripping, which induces epidermal barrier dysfunction; and the atopic march upon a subsequent airway challenge. Papain painting on ear skin and tape stripping cooperatively promoted dermatitis, the skin gene expression of proinflammatory cytokines and growth factors, up-regulation of serum total IgE, and papain-specific IgE/IgG1 induction. Epicutaneous sensitization induced T helper (Th) 2 cells and Th17 differentiation in draining lymph nodes. Ovalbumin and protease inhibitor-treated papain induced no or weak responses, whereas the co-administration of ovalbumin and papain promoted ovalbumin-specific IgE/IgG1 induction. Wild-type and IL-33-deficient mice showed similar responses in the epicutaneous sensitization phase. The subsequent airway papain challenge induced airway eosinophilia and maintained high papain-specific IgE levels in an IL-33-dependent manner. These results suggest that allergen source-derived protease activity and mechanical barrier damage such as that caused by scratching cooperatively promote epicutaneous sensitization and skin inflammation and that IL-33 is dispensable for epicutaneous sensitization but is crucial in the atopic march upon a subsequent airway low-dose encounter with protease allergens.

Topics: Allergens; Animals; Cell Differentiation; Cytokines; Dermatitis; Enzyme-Linked Immunosorbent Assay; Female; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Inflammation; Interleukin-33; Mice; Mice, Inbred C57BL; Ovalbumin; Papain; Protease Inhibitors; Real-Time Polymerase Chain Reaction; Skin; Stress, Mechanical; Th17 Cells; Th2 Cells; Wounds and Injuries

Reduced immune function is frequently a consequence of serious injury such as trauma-hemorrhage (T-H). Injury may lead to reduced T-cell activation, resulting in decreased engagement of costimulatory molecules after antigen recognition and in subsequent immunological compromise and anergy. We hypothesized that inhibition of CD28 expression is one possible mechanism by which immune functions are suppressed after T-H. Male C3H/HeN mice (with or without ovalbumin immunization) were subjected to sham operation or T-H and sacrificed after 24 hours. Splenic T cells were then stimulated with concanavalin A or ovalbumin in vivo or in vitro, and CD28, cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD69, and phospho-Akt expression was determined. T-cell proliferation/cytokine production was measured in vitro. Stimulation-induced CD69, CD28, and phospho-Akt up-regulation were significantly impaired after T-H compared with sham-operated animals; however, CTLA-4 expression was significantly higher in the T-H group. Over a 3-day span, stimulated T cells from sham-operated animals showed significantly higher proliferation compared with the T-H group. IL-2 and IFN-gamma were elevated in sham-operated animals, whereas IL-4 and IL-5 rose in the T-H group, revealing a shift from T(H)1 to T(H)2 type cytokine production after T-H. Dysregulation of the T-cell costimulatory pathway is therefore likely to be a significant contributor to post-traumatic immune suppression.

Topics: Animals; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; CD28 Antigens; CD4-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Concanavalin A; CTLA-4 Antigen; Cytokines; Enzyme Activation; Hemorrhage; Immune Tolerance; Lectins, C-Type; Lymphocyte Activation; Mice; Ovalbumin; Proto-Oncogene Proteins c-akt; Signal Transduction; Spleen; Wounds and Injuries

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Blood Glucose; Bradykinin; Dextrans; Hot Temperature; Injections, Intravenous; Insulin; Male; Ovalbumin; Polysaccharides; Rats; Wounds and Injuries