Endobronchial Inflammatory Myofibroblastic Tumor in a 3-Year-Old Child

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal tumor that can occur at any age. However, it is primarily seen in children, with the most common site being in the lung parenchyma, usually present with rare endobronchial lesions. This case reports the incidence in a 3-year-old girl diagnosed with pericardiac pneumonia treated with antibiotics with no clinical improvement. A chest computed tomography (CT) scan identified a 1.5-cm lesion in the left main bronchus. Bronchoscopy revealed complete obstruction of the left main stem bronchus. A left posterolateral thoracotomy was performed. Additionally, a left sleeve upper bronchial resection was conducted under fibroendoscopic control. Definitive histology confirmed IMT. After 2 years of endoscopic follow-up, there is no evidence of recurrence

Induction of selected cytokines and chemokines by OM-85 in MoDC.

<p><b>A</b>) MoDC (10⁶/ml) were stimulated with OM-85 as indicated and with 100 ng/ml LPS (IL-6, BAFF, CCL2, CXCL8 and CXCL6) or 10 ng/ml LPS (CCL3, CCL20 and CCL22) as a positive control. After 24 hours, supernatants were collected and analyzed by ELISA. Ut = untreated. *P<0.05 and **P<0.01 by Dunnett's Multiple Comparison Test. <b>B</b>) Supernatants of MoDC stimulated with OM-85 induce a G-protein-dependent migration of PMN. As a comparison, migration of PMN was elicited with unstimulated supernatants+CXCL8 and PMA. As expected, migration to CXCL8 was inhibited by both 10 nM M3 and 750 ng/ml, <i>Pertussis toxin</i> (P.Tox) while migration to PMA was not. Results are expressed as chemotactic index over migration to supernatants of unstimulated MoDC and represent means+/−SD of three independent Boyden chamber experiments. *P value<0.05 and ** P value<0.01 by Dunnett's Multiple Comparison Test.</p

Activation of PBMC and MoDC from COPD patients and healthy subjects by OM-85.

<p><b>A</b>) PBMC and <b>B</b>) MoDC (both 10⁶/ml) were stimulated as indicated in the presence or absence of 500 U/ml IFNγ or 100 ng/ml TNF-α. After 24 hours, supernatants were collected and analyzed by ELISA. Figure shows the results of healthy donors (open histograms) compared to COPD patients (black histograms). *P<0.05 by paired Student's <i>t</i> test.</p

Activation of the NF-kB and MAPK pathways by OM-85 in MoDC.

<p><b>A</b>) Immature human MoDC were stimulated with 100 µg/ml OM-85 for 30, 60, 90 and 120 minutes. 100 ng/ml LPS was used as a positive control. After cell lysis and protein fractionation, cytoplasmic (Cyto) and nuclear (Nuclei) extracts were blotted against NF-kB p65 and IkBα. β-actin and Lamin A/C represent loading controls for cytoplasmic and nuclear proteins respectively. The image depicts results obtained in one representative donor out of eight. <b>B</b>) EMSA (upper panel) and supershift (lower panel) showing the induction of NFkBp65-DNA binding activity by OM-85 in human moDC stimulated as in A). Signal specificity was assessed by competing each sample with a 125-fold excess unlabeled probe (lanes 2,4,6,8,10 upper panel). The image depicts results obtained in one representative donor out of four. <b>C</b>) OM-85 induces the production of luciferase in THP1 cells bearing a NF-kB-reporter plasmid (NF-kB pGL4, striped histograms). THP1 cells were stimulated with 1 µg/ml LPS and 1000 µg/ml OM-85. As expected, THP1 untransfected cells (untransfected, empty histograms) did not produce luciferase in response to stimulation. Similar results were obtained when cells were transfected with the pGL4 empty backbone (pGL4, black histograms). Results are expressed as mean+/−SD of three independent experiments. *P value<0.01 by Dunnett's Multiple Comparison Test. <b>D</b>) OM-85 activates the MAPK pathway. Cell extracts prepared as in A) were blotted with antibodies specific for phophorilated ERK1/2 (Cyto, upper panel) and total ATF2 and c-Jun (Nuclei, lower panel). β-actin and Lamin A/C represent loading controls for cytoplasmic and nuclear proteins respectively. The image depicts results obtained in one representative donor out of three. <b>E</b>) OM-85 induces NF-kB- and MAPK-dependent gene transcription. Immature MoDC were stimulated with 100 µg/ml OM-85 (open circles) and 100 ng/ml LPS (black circles) for 2, 4, 8 and 24 hours. After RNA extraction, reverse transcription and DNAse I digestion, samples were amplified by Q-PCR using gene-specific primers. Results represent means+/−SE of three independent donors and are expressed as fold induction (FI) over unstimulated samples (0).</p

Characteristic of COPD patients enrolled in the study.

<p>Table reports the main features (age, sex, age at diagnosis of COPD, disease stadium, therapy and notes) of selected patients <b>(P).</b></p

Synergism between OM-85 and pro-inflammatory agonists in MoDC.

<p>MoDC (10⁶/ml) were stimulated as indicated. After 24 hours, supernatants were collected and analyzed by ELISA. *P<0.05 and **P<0.005 by paired Student's <i>t</i> test.</p

Activation of primary DC subsets by OM-85.

<p><b>A</b>) MDC and <b>B</b>) PDC were isolated from buffy coats of three independent healthy donors and stimulated as indicated (10⁶/ml). After 24 hours, supernatants were collected and analyzed by ELISA. *P<0.05 by Dunnett's Multiple Comparison Test.</p