sVCAM-1 levels after segmental antigen challenge correlate with eosinophil influx, IL-4 and IL-5 production, and the late phase response.

Zangrilli, James; Shaver, Joseph R.; Cirelli, Rosemary; Cho, Seung Kil; Garlisi, Charles G.; Falcone, A.; Cuss, Francis M.; Fish, James E.; Peters, Stephen P.

doi:10.1164/ajrccm.151.5.7537586

Cited by 95 publications

(50 citation statements)

References 25 publications

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“…We also found that BAL fluid IL-5 correlated with the percentage of eosinophils in BAL and with the magnitude of the late-phase fall in FEV 1 . A correlation between BAL fluid IL-5 and eosinophil recruitment to the airway after segmental Ag challenge has been reported previously (38,(73)(74)(75)(76) and is consistent with the observation that anti-IL-5 therapy causes a significant decrease in sputum eosinophils (1).…”

Section: Discussionsupporting

confidence: 91%

Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge

Johansson¹,

Kelly

Busse

et al. 2008

The Journal of Immunology

117

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We hypothesized that there are clinically relevant differences in eosinophil integrin expression and activation in patients with asthma. To evaluate this, surface densities and activation states of integrins on eosinophils in blood and bronchoalveolar lavage (BAL) of 19 asthmatic subjects were studied before and 48 h after segmental Ag challenge. At 48 h, there was increased expression of αD and the N29 epitope of activated β1 integrins on blood eosinophils and of αM, β2, and the mAb24 epitope of activated β2 integrins on airway eosinophils. Changes correlated with the late-phase fall in forced expiratory volume in 1 s (FEV1) after whole-lung inhalation of the Ag that was subsequently used in segmental challenge and were greater in subjects defined as dual responders. Increased surface densities of αM and β2 and activation of β2 on airway eosinophils correlated with the concentration of IL-5 in BAL fluid. Activation of β1 and β2 on airway eosinophils correlated with eosinophil percentage in BAL. Thus, eosinophils respond to an allergic stimulus by activation of integrins in a sequence that likely promotes eosinophilic inflammation of the airway. Before challenge, β1 and β2 integrins of circulating eosinophils are in low-activation conformations and αDβ2 surface expression is low. After Ag challenge, circulating eosinophils adopt a phenotype with activated β1 integrins and up-regulated αDβ2, changes that are predicted to facilitate eosinophil arrest on VCAM-1 in bronchial vessels. Finally, eosinophils present in IL-5-rich airway fluid have a hyperadhesive phenotype associated with increased surface expression of αMβ2 and activation of β2 integrins.

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Section: Discussionsupporting

confidence: 91%

Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge

Johansson¹,

Kelly

Busse

et al. 2008

The Journal of Immunology

117

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Section: Discussionmentioning

confidence: 99%

“…In addition, mononuclear cells isolated from serum or BAL fluid samples from atopic asthmatic patients have been found to display an enhanced TH2-type cytokine response when activated by ligand. Moreover, emerging data derived from genetic analyses of family members with allergic asthma have demonstrated a significant direct correlation between altered airway responsiveness and IL-4 and IL-5 cytokine levels in serum or BAL fluid samples (5,19,28).The roles of the TH2 cytokines in allergic asthma have been reasonably well characterized. IL-4 was found to direct immunoglobulin isotype switching to IgE synthesis, and IL-5 was found to be primarily responsible for mast cell and eosinophil differentiation, recruitment, and activation (10-12).…”

mentioning

confidence: 99%

Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle

Hákonarson

Maskeri²,

Carter³

et al. 1999

J. Clin. Invest.

129

115

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CD4 + T helper (TH)1-and TH2-type cytokines reportedly play an important role in the pathobiology of asthma. Recent evidence suggests that proasthmatic changes in airway smooth muscle (ASM) responsiveness may be induced by the autocrine release of certain proinflammatory cytokines by the ASM itself. We examined whether TH1-and TH2-type cytokines are expressed by atopic asthmatic sensitized ASM and serve to autologously regulate the proasthmatic phenotype in the sensitized ASM. Expression of these cytokines and their receptors was examined in isolated rabbit and human ASM tissues and cultured cells passively sensitized with sera from atopic asthmatic patients or control subjects. Relative to controls, atopic sensitized ASM cells exhibited an early increased mRNA expression of the TH2-type cytokines, interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and their receptors. This was later followed by enhanced mRNA expression of the TH1-type cytokines, IL-2, IL-12, and interferon-γ (IFN-γ), as well as their respective receptors. In experiments on isolated ASM tissue segments (a) exogenous administration of IL-2 and IFN-γ to atopic asthmatic serum-sensitized ASM ablated both their enhanced constrictor responsiveness to acetylcholine (ACh) and their attenuated relaxation responsiveness to β-adrenoceptor stimulation with isoproterenol, and (b) administration of IL-5 and GM-CSF to naive ASM induced significant increases in their contractility to ACh and impaired their relaxant responsiveness to isoproterenol. Collectively, these observations provide new evidence demonstrating that human ASM endogenously expresses both TH1-and TH2-type cytokines and their receptors, that these molecules are sequentially upregulated in the atopic asthmatic sensitized state, and that they act to downregulate and upregulate proasthmatic perturbations in ASM responsiveness, respectively.J. Clin. Invest. 103:1077-1087 (1999. fluid levels of IL-4 and IL-5, as well as the percentage of cells expressing these cytokines, whereas IFN-γ levels and cells expressing IFN-γ in the lung are increased (22)(23)(24).Although this evidence implies an important role for CD4 + TH cells in the pathobiology of atopic asthma, we have recently demonstrated (25)(26)(27))that the ASM itself can be induced to express specific cytokines, notably IL-1β, in the atopic asthmatic sensitized state and, thereby, the ASM acts in an autocrine manner to manifest endogenously its proasthmatic phenotypic responsiveness. In view of the latter, together with the aforementioned implied role of an altered TH1/TH2 cytokine profile in allergic asthma, the present study examined whether isolated rabbit and human ASM (HASM) tissue and cultured ASM cells also express TH1-and TH2-type cytokines and their receptors, whether the expression of these molecules is perturbed in the atopic asthmatic sensitized state, and whether the latter perturbation is associated with proasthmatic changes in agonist-mediated ASM constrictor and relaxant responsiveness. The resu...

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“…The BAL sampling method potentially distorts the microvascular circulation of the lung and the barrier between the blood and air, both through physical trauma and the creation of diffusion gradients, and this is likely to vary substantially between individuals for purely technical reasons that cannot easily be quantified. This may be particularly important in the case of small molecular weight solutes, but it is clear that such considerations should be borne in mind by all groups interpreting the measurements of BAL solute levels, especially in the light of emergent interest in this area, with assays of cytokines [22], soluble adhesion molecules [23], and soluble markers of cellular activation in BAL fluid becoming technically routine [21,24].…”

Section: Discussionmentioning

confidence: 99%

Albumin is not suitable as a marker of bronchoalveolar lavage dilution in interstitial lung disease

Ward

Fenwick²,

Booth³

et al. 1997

Eur Respir J

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We have investigated the origin of raised bronchoalveolar lavage (BAL) albumin levels in interstitial lung diseases (ILDs), and the hypothesis that acute flux during BAL might contribute to the elevated levels of albumin in samples from ILD patients.Total albumin concentrations were measured in three separately aspirated 60 mL aliquots of BAL in 12 ILD patients and seven control subjects, and previous work indicating that BAL albumin levels may be raised in ILD was confirmed. In addition, the extent of acute flux from the circulation was investigated using 1.48 MBq of 125 I-radiolabelled human serum albumin injected intravenously shortly before the procedure.It was found that acute albumin flux occurred in only a minority of the ILD patients (4 out of 12) and control subjects (3 out of 7). These results indicate that the elevated levels of plasma proteins, such as albumin, documented in BAL aspirates from ILD patients are not an artefact of the BAL procedure related to increased vascular permeability, and that this finding is more likely to be related to the effects of chronic inflammatory changes in the lung due to the underlying disease.The work confirms that albumin is unsuitable as a denominator for the normalization of bronchoalveolar lavage solute results, since levels can vary, both as a result of acute flux and, more frequently, because of disease activity.

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sVCAM-1 levels after segmental antigen challenge correlate with eosinophil influx, IL-4 and IL-5 production, and the late phase response.

Cited by 95 publications

References 25 publications

Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge

Up-Regulation and Activation of Eosinophil Integrins in Blood and Airway after Segmental Lung Antigen Challenge

Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle

Albumin is not suitable as a marker of bronchoalveolar lavage dilution in interstitial lung disease

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