Effect of theophylline on CD11b and L-selectin expression and density of eosinophils and neutrophils in vitro

Spoelstra, Fokje M.; Berends, C.; Dijkhuizen, B.; Monchy, J. G. R. De; Kauffman, Hf

doi:10.1183/09031936.98.12030585

Cited by 25 publications

(20 citation statements)

References 29 publications

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“…1,2 In the presented patients, the increase in soluble selectins could not be induced by treatment as theophylline in vitro inhibited the L-selectin shedding induced by PAF on both eosinophils and neutrophils. 22 In the same way, increases in sE-selectin, kinins, and albumin after segmental allergen challenge of asthmatic subjects were inhibited by glucocorticoids. 23 It has been reported that increased soluble selectins could be a promising serological marker of the severity of inflammation in bronchial asthmatic children.…”

Section: Discussionmentioning

confidence: 66%

Elevation of serum soluble E‐selectin and VCAM‐1 in severe asthma

Hamzaoui

Ammar

et al. 2001

Mediators of Inflammation

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Objective: To investigate the significance of circulating adhesion molecules associated with leucocyteendothelial cell interactions in asthma, serum levels of soluble E (sE)-selectin, soluble P (sP)-selectin, soluble L (sL)-selectin, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in mild, moderate and severe asthma. Method: Serum levels of sE-selectin, sP-selectin, sLselectin, and sVCAM-1 were measured in 32 women with asthma and 30 healthy donors using an enzymelinked immunosorbent assay method. Twenty patients were suffering from severe asthma, and 12 from mild/moderate asthma. Results: Serum sE-selectin and sVCAM-1 levels from patients with asthma were significantly higher than those observed in healthy donors (p < 0.01). The levels of sP-selectin were the same as those of controls. The level of sE-selectin exhibited an important increase in the severe asthmatic patients compared with mild/moderate asthma (p < 0.01). The sVCAM-1 level was increased in severe asthma when compared with healthy controls. There was no correlation between the levels of soluble selectins and the age of the patients. A significant correlation was found between sE-selectin and sVCAM-1 levels. Conclusion: These data indicate that circulating soluble forms of the selectins may have different kinetics during the clinical course of asthma, suggesting that they may reflect different inflammatory pathways in severe asthma. Both sVCAM-1 and sE-selectin may be useful immunological markers for monitoring disease activity in asthma.Key words: Asthma, Inflammation, Selectins IntroductionAdherence of leucocytes to endothelial cells (EC) is a primordial event in the sequence of inflammatory response. Specific cell adhesion molecules, expressed on the surface of leucocytes and/or EC, have been identified. As an initial event during inflammation, leucocytes in the blood stream roll along EC with loose contact, mediated by E-selectin, P-selectin and L-selectin. 1 In the inflammation phase, activation of leucocyte integrins occurs with expression of immunoglobulin-like adhesion proteins on EC, including intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1). The leucocytes that are tightly bound to EC then migrate into the subendothelial tissue. Soluble forms of these adhesion molecules are released in circulation. Serum levels may be increased in several inflammatory diseases, and particularly in asthma. These circulating forms may be biologically active. 2 Asthma is known as a bronchial chronic inflammatory disorder. 3 Immunological abnormalities during asthma are characterized by marked activation of the immune system, leading to increased cytokine production by activated effector cells and the induction of antigen expression on EC. 4 The factors modulating the activation and recruitment of circulating inflammatory cells to the lung remain partially unknown, but an early step in this process is the interaction of adhesion molecules on circulating cells with those on EC. 5 Severe asthma is supposed t...

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Section: Discussionmentioning

confidence: 66%

Elevation of serum soluble E‐selectin and VCAM‐1 in severe asthma

Hamzaoui

Ammar

et al. 2001

Mediators of Inflammation

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“…It has been reported that theophylline attenuates the eosinophil expression of CD11b, a β 2 integrin molecule induced by platelet-activating factor [7, 9]. In the β 2 integrin-dependent adhesion of leukocytes, the activation states of this integrin may be more relevant than the number of molecules expressed on the cell surface.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Lim et al [3]found that theophylline reduced the number of eosinophils in sputa, biopsied specimens and bronchoalveolar lavage fluids in mild asthma. In this context, theophylline actually possesses a variety of in vitro effects on human eosinophils: induction of apoptosis [4, 5], inhibition of degranulation [5, 6, 7]and cell migration [8], and reduced surface expression of CD11b [6, 7, 9]or CD4 [8]. …”

Section: Introductionmentioning

confidence: 99%

Theophylline Attenuates the Adhesion of Eosinophils to Endothelial Cells

Choo¹,

Nagata²,

Sutani³

et al. 2003

Int Arch Allergy Immunol

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Background: Bronchial asthma is characterized by infiltration of eosinophils and other inflammatory cells into the airways. Binding to adhesion molecules expressed on endothelial cells is an initial step of eosinophil accumulation in the airways of asthmatic patients. Theophylline has been widely used in the treatment of bronchial asthma mainly due to its bronchodilating effect. It has recently been suggested that theophylline induces modulating effects on the survival or functional status of eosinophils. The objective of this study was to determine whether theophylline modifies the adhesive interaction between eosinophils and endothelial cells. Methods: Eosinophils were isolated from blood of patients with mild asthma. The effects of theophylline on eosinophil adhesion to human umbilical vein endothelial cells (HUVEC) or recombinant adhesion proteins were evaluated. The effect of theophylline on the expression of adhesion molecules on HUVEC was also examined. Results: Theophylline significantly inhibited the eosinophil adhesion induced by formyl-methionyl-leucil-phenylalanine (FMLP) or interleukine-5 (IL-5) at a concentration within the therapeutic range. The effect of theophylline on eosinophil adhesion was mimicked by rolipram, a selective phosphodiesterase inhibitor, and N6,2′-O-dibutyladenosine 3′5′-cyclic monophosphate (Db-cAMP; cAMP analogue). Finally, theophylline inhibited the expression of ICAM-1 and VCAM-1 on HUVEC stimulated with IL-4 plus TNF-α. Conclusion: Theophylline showed inhibitory effects on both the adhesive property of eosinophils and the expression of adhesion molecules on endothelial cells, thus suggesting that theophylline attenuates the adhesive interaction between eosinophils and endothelial cells.

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“…Segmental lung antigen challenge upregulates and activates eosinophil integrins in blood and airways of asthmatics (62). From studies in the 1990s it is known that PDE4 inhibition and theophylline can rapidly reduce the expression of CD11b in neutrophils and eosinophils (63,64). BAL eosinophils and neutrophils showed no differences in CD11b phenotype when they were obtained from mice lacking PDE3A or PDE3B or WT ( Figure 7, A and B).…”

Section: Pde3a -/-And Pde3b -/-Mice Show Reduced Albumin Leakage In Amentioning

confidence: 99%