M. Laviolette

OX40L blockade and allergen‐induced airway responses in subjects with mild asthma

The OX40/OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells.

Influence of smoking on airway inflammation and remodelling in asthma

Background Although exposure to tobacco smoke has been associated with increased morbidity and mortality, cigarette smoking is still common in the asthmatic population. Induced sputum neutrophilia has been observed in asthmatic smokers, but the effects of regular smoking on their bronchial mucosa morphology remain to be defined. This study documents the inflammatory and remodelling features in bronchial biopsies of smoking compared with non‐smoking asthmatics.

Interleukin-4 production by human alveolar macrophages

Background IL‐4 is a key factor for T helper type 2 (Th2) differentiation and Ig class switching to IgE and IgG4 during the development of immune responses. IL‐4 is produced by T cells, mast cells, basophils, and eosinophils. However, there is also evidence suggesting that rat alveolar macrophages (AMs) produce IL‐4.

Bronchial inflammation in corticosteroid‐sensitive and corticosteroid‐resistant asthma at baseline and on oral corticosteroid treatment

Background Pathophysiology of corticosteroid (CS)‐resistant asthma remains incompletely understood.

Effect of salmeterol on allergen‐induced airway inflammation in mild allergic asthma

A previous study suggested that the long‐acting β2‐adrenergic agonist salmeterol (SM) had inhibitory effects on bronchial mucosal inflammation 6 hours after allergen exposure.

Endothelial cells modulate eosinophil surface markers and mediator release

Migration from blood to tissue modulates eosinophil function, possibly through interactions with endothelial cells. The effects of contact with and migration through endothelial cells on eosinophil expression of surface markers and release of leukotriene C4 were evaluated. A small proportion (2.6%) of eosinophils spontaneously migrated through endothelial cell monolayers. Activation of endothelial cells by interleukin (IL)-4 or IL-1β slightly increased this migration (to 12.4%), which became much greater when a chemoattractant was placed in the lower chamber (84.3%). However, the chemotactic effect was downregulated by pretreating endothelial cells with interferon gamma (IFN-γ; 63.1%). At baseline, 5% of eosinophils expressed CD69; this increased to 30.7% in culture on untreated endothelial cells and to 50.9% on IL-1β-pretreated endothelial cells. This effect was mediated through intercellular adhesion molecule-1/CD11b interaction. Eosinophil migration through endothelial cells further increased CD69 expression to 63.9% and also increased CD35 expression from 83.3 to 91.3%. Upon stimulation, eosinophils that had migrated through endothelial cells produced more leukotriene C4 than control cells (872.4 and 103.9 pg·mL−1, respectively). Endothelial cell pretreatment with IL-4 or IL-1β further increased leukotriene C4 release (1,789.1 and 2,895.1 pg·mL−1, respectively), whereas pretreatment with IFN-γ decreased it (293.7 pg·mL−1). These data show that in vitro interactions with endothelial cells upregulate eosinophil membrane receptor expression and mediator release and that these effects are differently modulated by T-helper cell type 1 and 2 cytokines. These eosinophil modulations may play an important role in asthma pathogenesis.

Migration through basement membrane modulates eosinophil expression of CD44

Background Tissue eosinophils express more membrane receptors and release more mediators than blood eosinophils, suggesting that migration from blood to tissue modulates eosinophil phenotype and functions.

Increased expression of intercellular adhesion molecule‐1 (ICAM‐1) in a murine model of pulmonary eosinophilia and high IgE level

T lymphocytes and eosinophils are probably involved in the pathogenesis of allergic broncho‐pulmonary aspergillosis (ABPA), a disease characterized by pulmonary eosinophilia and high serum and lavage IgE levels. We recently developed a murine model of ABPA. To investigate the mechanisms of T lymphocyte and eosinophil recruitment to the lung in this disease, we examined the expression of ICAM‐1 In the lung tissue of mouse challenged with Aspergillus fumigatus (Af) antigen. C57B1/6 mice were intranasally exposed to Af (Af group) or saline (control group) three times a week for 1, 2 or 3 weeks. On days 4, 7, 14 and 21, mice were killed and lung tissue was fixed in acetone and embedded in glycol methacrylate. Serial μm sections were stained with chromotrope 2R and MoAbs against ICAM‐I. CD11a/CD18 (LFA‐1) and CD3. Af‐challenged mice presented significant increases in eosinophil, T lymphocyte and LFA‐1‐positive cell count and up‐regulated expression of ICAM‐1 in the lung tissue at all the time points examined. ICAM‐1 expression intensity correlated with the number of T lymphocytes (r= 0·59, P <0·01), LFA‐1‐positive cells (r= 0·68, P < 0·001), but not of eosinophils (r=−0·24, P > 0·05). These findings suggest that up‐regulation of ICAM‐1 expression is involved in the inflammatory process of this murine model of ABPA, and that this up‐regulation may be more relevant to the T lymphocyte accumulation in the lung.

Variability of Inflammatory Cell Counts on Bronchial Biopsies of Normal Subjects

Bronchial biopsies are currently used to study the pathophysiology of airway diseases, and comparisons are often made with biopsies from healthy volunteers. It is therefore important to evaluate the variability in each parameter analyzed in bronchial biopsies of healthy volunteers in order to be able to discriminate significant changes. We analyzed bronchial biopsies of 31 nonsmoking, nonatopic healthy subjects who volunteered as normal controls for studies on pathophysiology of asthma. Mean % epithelial desquamation was 23.7% of observed total epithelial length. No subepithelial fibrosis was observed. Inflammatory cell counts (/mm2 connective tissue surface) were variable among subjects but not different between small (≤0.25 mm2) and large biopsies. Medians (range) of positive cells were for CD3: 20.5 (0–530.0), CD4: 6.2 (0–124.4), CD8: 1.8 (0–81.5), CD25: 0 (0–62.3), HLA-DR: 80.0 (3.5–524.2), EG1: 5.3 (0–180.6), EG2: 6.4 (0–48.8), AA1: 51.3 (0–286.4), CD45: 39.7 (0–448.5) and CD45ro: 28.6 (0–425.2). Subjects living in an urban area had significantly higher CD8-positive cell counts than those from suburban areas (p = 0.0001). The presence of an animal at home was associated with lower positive cell counts for CD4 (p = 0.02), CD45 (p = 0.02) and HLA-DR (p = 0.01). In conclusion, the variability in the number and expression of markers of activity of bronchial immune cells in normal subjects likely reflects variable host responses to environmental exposures and must be taken into account when compared to specimens obtained in subjects with airway diseases.