Patterns of reactivity to lipid transfer proteins of plant foods and Artemisia pollen: an in vivo study

BACKGROUND: Lipid transfer proteins (LTPs) are major allergens of Rosaceae fruits in the Mediterranean area. IgE-cross-reactivity has been demonstrated in vitro among LTPs from peach, apple, chestnut and Artemisia pollen. The aim of this study was to evaluate the reactivity to LTPs from peach, apple, chestnut and Artemisia pollen by means of skin prick tests (SPTs). METHODS: Forty-seven patients allergic to peach (peach group), 20 patients sensitized to Artemisia pollen with no food allergies (Artemisia group), and 12 control subjects were skin tested with fresh peach, as well as with whole extracts and purified LTPs of peach, apple, chestnut and Artemisia pollen. RESULTS: The rates of positive SPTs for peach, apple, chestnut and Artemisia LTPs were, respectively, 91, 77, 23, and 36% in the peach group, and 30, 5, 15 and 40% in the Artemisia group. No response was observed in the control subjects. SPTs with peach LTP strongly correlated with SPTs conducted with fresh peach. In the peach group, the most frequent pattern of reactivity to LTPs was the combination peach-apple (45%), followed by peach-apple-Artemisia-chestnut (21%). Significant correlations were found between peach and apple LTPs, and between Artemisia and chestnut LTPs. Positive SPTs to chestnut LTP were only observed in patients with positive SPTs to Artemisia LTP. All the patients with positive case histories to chestnut reacted to chestnut LTP. CONCLUSIONS: LTPs are plant panallergens with different patterns of cross-reactivity. They are major allergens of Rosaceae fruits and seem to be involved in allergic reactions to unrelated foodstuffs such as chestnut, probably through sensitization to the cross-reactive Artemisia LTP. Rosaceae LTPs could be useful tools for in vivo diagnosis of Rosaceae fruit allergy.     

Prophylaxis and treatment of experimental lung metastases in mice after treatment with liposome-encapsulated 6-O-stearoyl-N-acetylmuramyl-L-α-aminobutyryl-D-isoglutamine

A new lipophilic muramyl dipeptide analog, 6-O-stearoyl-N-acetylmuramyl-L--aminobutyryl-D-isoglutamine, when incorporated in liposomes, was effective in both the prevention and eradication of experimental pulmonary metastases in mice. Multilamellar vesicles composed of synthetic phospholipids (phosphatidylglycerol and phosphatidylcholine) containing saturated myristoyl or unsaturated dioleoyl acyl chains were found to potentiate the antimetastatic activity of this glycopeptide. Prophylactic and therapeutic efficacy was observed against the three murine tumors tested: FSa, an immunogenic fibrosarcoma; NFSa, a nonimmunogenic fibrosarcoma; and B16 melanoma. Neither the administration of empty liposomes or free glycopeptide, nor their coadministration, had a significant antimetastatic effect. This approach is promising for the therapy of cancer metastases in humans, particularly in the prevention of metastatic seeding and in the treatment of micrometastases.This is contribution No. 180 from the Institute of Bio-Organic Chemistry, Syntex Research.     

The effect of immunotherapy on eosinophil accumulation and production of eosinophil chemotactic activity in the lung of subjects with asthma during natural pollen exposure

Two groups of birch pollen--allergic patients with seasonal rhinoconjunctivitis and asthma were followed during two consecutive birch-pollen seasons, one group, N = 10, during a season with high pollen load, and one group, N = 15, during a season of low pollen load. Half the patients were treated with immunotherapy (IT) for 3 and 4 years, respectively. The other half of the patients served as control group (non-IT). Bronchoalveolar lavage (BAL) was performed once before each season and once during the pollen season. Eosinophil (EOS) numbers in BAL were increased (p less than 0.01) during the season with high pollen load but not in the season with a low pollen load, and this increment was absent in the IT-treated group. Also, the EOS cationic protein levels were raised in the non-IT-treated group during the season with a high pollen load. The levels of EOS and neutrophil chemotactic activity were raised in BAL in both seasons in the non-IT-treated group compared with the IT-treated group (p less than 0.02, p less than 0.003, p less than 0.04, and p less than 0.005 in high- and low-load pollen season, respectively). Serum and BAL eosinophil chemotactic activity (ECA) were positively correlated (p less than 0.001). We conclude that there is an influx of active EOSs into the lung of pollen-allergic patients with asthma during a pollen season, which may be abrogated by IT. Furthermore, the generation of ECA appears to be an extremely sensitive marker of antigenic exposure, and the potent inhibition of the generation of ECA by IT may provide a clue as to the mechanism of this treatment.     

Ratio of shear to load ground-reaction force may underlie the directional tuning of the automatic postural response to rotation and translation

This study sought to identify the sensory signals that encode perturbation direction rapidly enough to shape the directional tuning of the automatic postural response. We compared reactions to 16 directions of pitch and roll rotation and 16 directions of linear translation in the horizontal plane in freely standing cats. Rotations and translations that displaced the center of mass in the same direction relative to the feet evoked similar patterns of muscle activity and active ground-reaction force, suggesting the presence of a single, robust postural strategy for stabilizing the center of mass in both rotation and translation. Therefore we postulated there should be a common sensory input that encodes the direction of the perturbation and leads to the directional tuning of the early electromyographic burst in the postural response. We compared the mechanical changes induced by rotations and translations prior to the active, postural response. The only consistent feature common to the full range of rotation and translation directions was the initial change in ground-reaction force angle. Other variables including joint angles, ground-reaction force magnitudes, center of pressure, and center of mass in space showed opposite or nonsignificant changes for rotation and translation. Change in force angle at the paw reflects the ratio of loading force to slip force, analogous to slips during finger grip tasks. We propose that cutaneous sensors in the foot soles detect change in ground-reaction force angle and provide the critical input underlying the directional tuning of the automatic postural response for balance.     

Gene profiling reveals increased expression of uteroglobin and other anti-inflammatory genes in glucocorticoid-treated nasal polyps

BACKGROUND: Treatment with local glucocorticoids (GCs) decreases symptoms and the size of nasal polyps. This might depend on the downregulation of proinflammatory genes, as well as the upregulation of anti-inflammatory genes. OBJECTIVE: We sought to identify GC-regulated anti-inflammatory genes in nasal polyps. METHODS: Affymetrix DNA microarrays were used to analyze the expression of 22,283 genes in 4 nasal polyps before and after local treatment with fluticasone (400 microg/d). Expression of uteroglobin and mammaglobin B was analyzed with real-time PCR in 6 nasal polyps and in nasal biopsy specimens from 6 healthy control subjects. RESULTS: Two hundred three genes had changed in expression in treated polyps, and 139 had known functions: 54 genes were downregulated, and 85 were upregulated. Genes associated with inflammation constituted the largest single functional group. These genes affected key steps in inflammation (eg, immunoglobulin production; antigen processing and presentation; and the chemoattraction and activation of granulocytes, T cells, and B cells). Several proinflammatory genes were downregulated. In contrast, some anti-inflammatory genes were upregulated. The gene that increased most in terms of expression was uteroglobin. This was confirmed with real-time PCR. By contrast, expression of uteroglobin was lower in untreated polyps than in healthy nasal mucosa. Immunohistochemical investigation showed staining of uteroglobin in the epithelium and in seromucous glands in control subjects and in nasal polyps. CONCLUSION: Upregulation of anti-inflammatory genes, such as uteroglobin, might contribute to the effects of local treatment with GCs in nasal polyps.