Lung structure and function of infants with recurrent wheeze when asymptomatic.

Infants with recurrent wheeze have repeated episodes of airways obstruction; however, relatively little is known about the structure and function of their lungs when not symptomatic. The current authors evaluated whether infants with recurrent wheeze have smaller airway lumens or thickened airway walls, as well as decreased airway function. High-resolution computed tomography images 1 mm thick were obtained at three anatomic locations at an elevated lung volume and at functional residual capacity. Forced expiratory flows were also measured in subjects with recurrent wheeze. Airway lumen, wall areas and lung tissue density were not significantly different for recurrent wheeze (n = 17) and control (n = 14) subjects; however, subjects with recurrent wheeze had lower forced expiratory flows than predicted. Similar findings were obtained when subjects were grouped by exposure to tobacco smoke. These findings indicate that infants with recurrent wheeze, as well as exposure to tobacco smoke, have lower airway function when not symptomatic. The lower forced expiratory flows may result from a degree of airway narrowing that could not be resolved with the methodology employed or from other mechanisms, such as more collapsible airways or decreased pulmonary elastic recoil.

Lymphocyte accumulation during Pseudomonas aeruginosa-induced pneumonia in rodents does not require CD11a and intercellular adhesion molecule-1.

During Pseudomonas aeruginosa-induced pneumonia in rodents, the acute infiltrate of neutrophils is followed by accumulation of lymphocytes in the perivascular connective tissue. The roles of the adhesion molecules CD11a/CD18 and intercellular adhesion molecule-1 (ICAM-1) in this accumulation of lymphocytes were investigated. The numbers of lymphocytes in P. aeruginosa-induced pneumonia were compared in animals treated with blocking antibodies to either CD11a, ICAM-1, IgG, or no antibody. In other experiments, the lymphocyte accumulation during P. aeruginosa-induced pneumonia in ICAM-1 mutant mice was compared with that in wild-type mice. In rats, both a murine anti-rat CD11a antibody and nonspecific murine IgG partially inhibited the lymphocyte accumulation by 30 to 40% compared with animals that received no antibodies. In mice, blocking antibodies to either CD11a or ICAM-1 did not decrease the lymphocyte accumulation compared with mice given IgG or no antibody. Further, there was no attenuation of the lymphocyte accumulation induced by P. aeruginosa in the ICAM-1 mutant mice compared with wild-type mice, either in the total number of lymphocytes or the number of CD4+, CD8+, or B cells. We conclude that neither CD11a/CD18 nor ICAM-1 are required for lymphocyte accumulation during P. aeruginosa-induced pneumonia in rodents. The partial inhibition of the lymphocyte accumulation in both the anti-CD11a- and IgG-treated rats may be due to nonspecific effects of foreign proteins on cellular functions.

Effect of protein synthesis inhibition by cycloheximide on lymphocyte circulation.

BACKGROUND: Lymphocyte recirculation is directed by glycoprotein adhesion molecules on lymphocytes and endothelial cells of lymphoid tissues. Lymphocyte circulation in different lymphoid tissues is dependent on the type of glycoprotein adhesion molecules present. In the present study, the effects of inhibiting new protein synthesis on the ability of lymphocytes to circulate and home to different lymphoid tissues was investigated. EXPERIMENTAL DESIGN: New Zealand White rabbits and Lewis white rats were treated with cycloheximide or buffer. Total circulating lymphocyte counts and lymphocyte subsets were measured. Rabbits were given autologous, 111indium-labeled lymphocytes to determine if there were changes in the organ distribution of lymphocytes after cycloheximide treatment. RESULTS: After cycloheximide treatment, the number of circulating lymphocytes but not neutrophils increased significantly by 2 hours in both rabbits and rats. T cells, B cells, and L-selectin-positive lymphocytes showed similar increases. Measurements of the distribution of the radiolabeled, autologous lymphocytes in cycloheximide-treated animals showed significantly greater numbers circulating in the peripheral blood and decreased numbers in Peyer's patches, mesenteric lymph nodes, and spleens compared with controls. In contrast, the number of radiolabeled lymphocytes in the lung was not decreased after cycloheximide administration. CONCLUSIONS: These results indicate that protein synthesis inhibition causes lymphocytosis due to decreased lymphocyte homing to mesenteric nodes, Peyer's patches, and spleen, but not lung. This effect was not specific for distinct lymphocyte subsets, including T cells, B cells, or lymphocytes expressing L-selectin. These data show that molecules modulating lymphocyte homing in some organs have rapid turnover rates and suggest that changes in homing during the inflammatory process can be rapidly regulated by changes in protein translation.

Effect of hypoxia on endothelin-1 production by pulmonary vascular endothelial cells.

Endothelin-1 (ET-1), a peptide product of endothelial cells, is mitogenic for fibroblasts and smooth muscle cells. In this study we examined the effect of hypoxia on ET-1 production by bovine pulmonary vascular endothelial cells. Bovine pulmonary artery (BPAE) and microvascular endothelial (BMVE) cells were isolated, grown in tissue culture, and characterized by the presence of Factor VIII related antigen and LDL uptake. Baseline production of ET-1 by BPAE cells (measured by radioimmunoassay) increased over time. BMVE cells produced one tenth the amount of ET-1 as produced by the pulmonary artery endothelial cells under the same conditions. In both cell types, hypoxia (0% O2) significantly reduced the amount of ET-1 at 48 h. Restoration of normoxia in 21% O2 for 48 h resulted in a return of ET-1 levels to baseline. Northern blot analysis showed decreased ET-1 mRNA in cells exposed to hypoxia for 48 h. These data demonstrate that pulmonary vascular endothelial cells respond to hypoxia by reversibly decreasing ET-1 production, and this attenuation is likely regulated at the level of transcription.