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P Guardia

Publications and source records attributed to P Guardia.

At least 19 recordsLinked to original sources
PubMed2005

L-selectin expression on neutrophils from allergic patients.

BACKGROUND: L-selectin (CD62L) is an adhesion molecule involved in leucocyte attachment to endothelium at sites of inflammation, and it has been demonstrated that L-selectin is rapidly shed after neutrophil activation. Recently, it has been reported that there is increasing evidence of neutrophil participation in asthma and the allergic process. OBJECTIVE: The present study was designed to determine whether an IgE-dependent mechanism can modulate L-selectin expression on the surface of neutrophils. Moreover, we analyse the potential implication of intracellular signal-transduction pathways and whether specific immunotherapy (IT), glucocorticoids and antihistamines might regulate this process. METHODS: Peripheral blood neutrophils from three groups of donors (asthmatic group without IT treatment, IT-treated asthmatic group and healthy group) were used. Cells were challenged in vitro with the specific allergen that produced clinical symptoms in asthmatic patients and also with the allergen to which the patients were not sensitive. Neutrophils from healthy donors were also challenged with allergens. Expression of CD62L on the neutrophil surface was analysed by flow cytometry, and soluble CD62L (sCD62L) in culture supernatant by ELISA. In an attempt to discover which IgE receptor is involved, we also challenged the neutrophils with monoclonal antibody to FcepsilonRI, FcepsilonRII (CD23) and galectin-3 receptors. RESULTS: When neutrophils from allergic patients were challenged with specific allergens that produce clinical allergy symptoms, L-selectin was down-regulated from the surface of those cells, accompanied by a concomitant up-regulation of soluble L-selectin in the supernatant. The challenge with antibodies against FCepsilonRI, FCepsilonRII (CD23) and galectin-3, induces down-modulation of L-selectin on the surface of the neutrophils in all three cases. Calphostin C, wortmannin and manoalide attenuated CD62L down-regulation, suggesting the potential implication of protein kinase C, phosphatidylinositol 3-kinase and phospholipase A(2) in the process. IT and glucocorticoids modulated allergen-dependent CD62L down-regulation, whereas antihistamines (terfenadine, loratadine and cetirizine) or nedocromil sodium did not affect the shedding of L-selectin. CONCLUSIONS: We present evidence that the neutrophil surface expression of CD62L can be modulated by an allergen-dependent mechanism. The modulation of CD62L expression can be induced through the three receptors of IgE. This process can be affected by IT.

Adolescent↗
PubMed2003

Allergen-dependent CD14 modulation and apoptosis in monocytes from allergic patients.

BACKGROUND: CD14 is a most important monocyte surface molecule. Recently, it has been reported that there is an important relationship between CD14 and immunoglobulin E, and that regulation of CD14 expression is an effector mechanism mediating apoptosis of monocytes. OBJECTIVE: The present study was designed to determine whether specific allergens were able to modulate CD14 expression and apoptosis by monocytes from allergic patients or whether specific immunotherapy (IT) might affect these processes. METHODS: One group of adult allergic asthmatic patients had received IT for the previous 3 years. Another similar group was not treated with IT. We challenged peripheral blood monocytes from both groups of asthmatic patients in vitro with the specific allergen that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Monocytes from normal subjects were also challenged with allergens. Expression of CD14 on the monocyte surface was analyzed by flow cytometry, and soluble CD14 (sCD14) in culture supernatant by enzyme-linked immunosorbent assay. The three groups of subjects were challenged with allergens, and apoptosis was analyzed by flow cytometry. RESULTS: When monocytes from non-IT-treated asthmatic patients were cultivated with the allergens to which the patients were sensitive, a significant up-regulation on the monocyte surface was observed compared with results from the healthy group (P < 0.003) and from the IT asthmatic group (P < 0.003). A significantly higher sCD14 level was observed in the culture supernatant of the monocytes from the IT asthmatic group were observed compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (P < 0.001). A significantly higher apoptosis level was observed in monocytes from the IT asthmatic group compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (<0.001). CONCLUSIONS: We present evidence that the expression of CD14 on the surface of monocytes and the apoptosis of the same cells can be modulated by an allergen-dependent mechanism. These processes can be affected by IT.

Adult↗
PubMed2003

Tolerance of a cluster schedule on the treatment of seasonal allergic respiratory disease with pollen extracts quantified in mass units.

In order to evaluate the tolerance of a cluster schedule on specific immunotherapy (SIT), 306 patients were included in a multicenter study. The patients were suffering from rhinoconjunctivitis with/without asthma, caused by sensitization to olive and/or grass pollen. SIT was administered subcutaneously according to a cluster schedule in which the maintenance dose is reached after four visits (3 weeks). The extracts were biologically standardized with major allergens quantified in mass units. Local reactions appeared in 7.2% of the patients and 1.3% of the doses. Systemic reactions (SR) were recorded in 1.2% of the doses administered to 9.5% of the patients. No anaphylactic shock was registered, and all the SR responded fully and rapidly to treatment. There was no difference in SR according to diagnosis or allergen extract used. The majority of SR occurred with the administration of vial of higher concentration (Vial 2: 7 SR (22%), Vial 3: 32 SR (78%), p < 0.05). Of the 32 SR recorded with Vial 3, 13 (41%) were immediate, with no existing association between dose administered and appearance of SR. However, of the 18 delayed SR (56%), 14 occurred after the administration of the first two doses of Vial 3 and four occurred after administration of the second two doses (78% vs 22%, p < 0.05). On the other hand, this regime realized an important saving in cost and time compared to the conventional schedule (1581 fewer doses and 2754 fewer visits were necessary to reach the optimal dose). Considering all these factors, the clinical profile of the proposed regime may be qualified as good. However, future studies are necessary in order to better adjust the schedule to avoid the delayed SR that occurred after the administration of the first two doses of Vial 3.

Adult↗
PubMed2002

Respiratory burst in neutrophils from asthmatic patients.

BACKGROUND: The role of oxygen radicals has been implicated in disease processes of asthma. We have previously shown that specific allergens were able to activate respiratory burst by neutrophils from allergic patients sensitized to allergens of the same type as those which produce clinical allergy. OBJECTIVES: In this study, we attempted to evaluate the production of respiratory burst by an anti-IgE Ab in neutrophils from asthmatic allergic patients (with and without immunotherapy treatment) and in neutrophils from healthy subjects. METHOD: Neutrophils were stimulated by 10 microg/mL of anti-IgE Ab for 15 min at 37 degrees C. The production of respiratory burst from neutrophils was assayed by luminol-amplified chemiluminescence method. RESULTS: The respiratory burst was significantly higher in neutrophils from non-IT-asthmatic patients than in neutrophils from both healthy (p < 0.001) and IT-asthmatic (p < 0.001) groups. The IT-asthmatic group presented levels of respiratory burst approximately equal to those from non-allergic subjects (p=0.426). CONCLUSIONS: We conclude that neutrophils obtained from allergic asthmatic patients have an increased propensity to generate respiratory bursts, in comparison with neutrophils from healthy subjects. Immunotherapy actively modifies the respiratory burst by neutrophils from allergic asthmatic patients.

Antibodies↗
PubMed1996

Enhancement of Antigen-specific functional responses by neutrophils from allergic patients.

It has been demonstrated that neutrophils from healthy donors or from patients with inflammatory disorders can bind immunoglobulin (Ig) E proteins through binding to Mac-2/epsilon bp. Functional responses to allergens were assessed by measuring the respiratory burst and intracellular Ca2+ levels, and binding of allergens to neutrophils was assessed by flow cytometry analysis and fluorescence microscopy. In this article, we demonstrate that neutrophils sensitized to specific allergens (from allergic patients), but not from healthy donors, are sensitive to allergens of the same type as those that produce clinical allergic symptoms. The activation of neutrophils was analyzed by the induction of a respiratory burst that was detected with luminol-dependent chemiluminescence. Intracellular Ca2+ levels increased parallel to those of the inducing allergens. In addition, the specific binding of allergens on the cell surface was revealed by flow cytometry and allergen-FITC-labeled staining analyses. The present data suggest a restricted recognition of allergen by sensitive neutrophils, probably associated with the specific binding of the allergen to its corresponding IgE molecule, which is bound to the Mac-2/epsilon bp structure. These findings demonstrate a functional role of allergen-associated neutrophils during the allergic state.

Allergens↗
PubMed1995

Peripheral blood T lymphocytes in seasonal bronchial asthma.

Variations in T lymphocytes in asthmatic patients are related to disease severity. However, the effects of natural exposure to pollens on peripheral blood T lymphocytes have not been clarified. In this paper, the effects on peripheral blood CD4 and CD8 lymphocytes from pollen-sensitive subjects and from nonatopic donors were studied during and outside the pollen season. In patients who suffer from seasonal asthma, we found an increase in the CD4/CD8 bright ratio and a decrease in the mean number of CD4 receptors per cell during the pollen season. No variation was observed in healthy subjects. These results suggest that CD4 lymphocytes may be causally linked to the pathogenesis of seasonal bronchial asthma.

Adolescent↗
PubMedDate not supplied

Clustered schedules in allergen-specific immunotherapy.

BACKGROUND: Injective immunotherapy is traditionally performed with a build-up phase lasting 3 to 4 months. The costs, decreasing compliance from both patients and clinicians and inconveniences due to this schedule may be overcome using different schedules. METHODS AND RESULTS: A revision of the published papers with clustered schedules has been made. Attention has been focussed on tolerance and its relationships with relevant parameters such as kind of extract (aqueous or depot), allergens and their pharmaceutical presentation, schedule followed, use or not of a premedication, clinical manifestations of patients before treatment. For a better revision, papers dealing with clustered schedules have been divided into two groups. The first group includes 20 papers not designed to study the clustered schedule but using it to study other parameters affected by specific immunotherapy. The second group includes 9 papers specifically or mainly designed to study the clustered schedule. A huge difference in the rate of side effects could be assessed among different papers, even in studies run with similar allergens from the same producer and with a similar schedule. CONCLUSIONS: Summarizing the results of the revision, the following conditions seem to lead to the optimal tolerance of the clustered schedule: use of a premedication; use of a depot preparation; use of no more than 4 administrations per cluster; administration of 1-2 clusters per week and of 4 to 6 clusters in total. These results seem promising but further efforts are required to better define the optimal clustered schedule.

Allergens↗
PubMedDate not supplied

Tolerance and short-term effect of a cluster schedule with pollen-extracts quantified in mass-units.

We performed a prospective, multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season. The study was carried out in eight centers and included 191 patients (children and adults) with allergic respiratory disease due to sensitization to olive tree and/or grass pollen. Of these, 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits. After 3 months of treatment, significant differences were found between the two groups in medication consumption (antihistamines in drops and oral formulations: p = 0.045 and p = 0.001, respectively; short-acting beta2-agonist treatments: p = 0.004) and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014, respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon [IFN-gamma], and tumor necrosis factor [TNF-alpha]) was determined before the start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5 and 10 (Th2 profile) decreased while those of IL-2, IFN-gamma, and TNF-alpha (Th1 profile) decreased. These differences were more marked in the active group than in the control group but were not statistically significant. No severe adverse effects were recorded. This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment. A double-blind, placebo-controlled study is needed to confirm these results.

Adult↗
PubMedDate not supplied

Variations of the cellular antigens CD4 and CD8 in pollinic patients during the spring.

In order to study the possible variations of CD4 and CD8 antigens in pollinic patients, we have studied 25 individuals (11 rhinoconjunctivitis and 14 rhinoconjunctivitis-asthma) before (T0), in the middle (T1) and after the spring (T2). The number of receptors per cell of CD4 start from values in T0, decrease in T1 and increase at the end of the spring (p < 0.00001), which could represent a mechanism to limit the clonal response to an antigen. An increase in the CD4/CD8 bright ratio could be indicate a higher helper mechanism in T1 with respect to T0 and T2 (p < 0.01). The opposite meaning is to given to the increase of CD8bright receptors in the asthmatic patients, and not only in those who suffer only from a rhinopathy (the only difference between the two groups of patients) during T2 over the T1 (p < 0.00001). The greater number of lymphocytes CD8 dim + during T1 with respect to T2 (p < 0.009) and the increase in the number of receptors of such cells during T1 with respect to T2 (p < 0.00001) suggests a possible intervention of these cells in the regulation of the response of the B and T lymphocytes. Of the two soluble factors CD4 (sCD4) and CD8 (sCD8), only the sCD4 increases during T1 (p < 0.0001) in an inverse manner as occurs with CD4 cell receptors, while the sCD8 remains unchanged during the three periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗