Macrophage-polarizing stimuli differentially modulate the inflammatory profile induced by the secreted phospholipase A2 group IA in human lung macrophages.

In this study we investigated the effects of snake venom Group IA secreted phospholipase A2 (svGIA) on the release of inflammatory and angiogenic mediators from human lung macrophages (HLMs). HLMs were incubated with lipopolysaccharide (LPS) or svGIA with or without macrophage-polarizing stimuli (IL-4, IL-10, IFN-γ or the adenosine analogue NECA). M2-polarizing cytokines (IL-4 and IL-10) inhibited TNF-α, IL-6, IL-12, IL-1ß, CXCL8 and CCL1 release induced by both LPS and svGIA. IL-4 inhibited also the release of IL-10. IFN-γ reduced IL-10 and IL-12 and increased CCL1 release by both the LPS and svGIA-stimulated HLMs, conversely IFN-γ reduced IL-1ß only by svGIA-stimulated HLMs. In addition, IFNγ promoted TNF-α and IL-6 release from svGIA-stimulated HLMs to a greater extent than LPS. NECA inhibited TNF-α and IL-12 but promoted IL-10 release from LPS-stimulated HLMs according to the well-known effect of adenosine in down-regulating M1 activation. By contrast NECA reduced TNF-α, IL-10, CCL1 and IL-1ß release from svGIA-activated HLM. IL-10 and NECA increased both LPS- and svGIA-induced vascular endothelial growth factor A (VEGF-A) release. By contrast, IL-10 reduced angiopoietin-1 (ANGPT1) production from activated HLMs. IFN-γ and IL-4 reduced VEGF-A and ANGPT1 release from both LPS- and svGIA-activated HLMs. Moreover, IL-10 inhibited LPS-induced ANGPT2 production. In conclusion, we demonstrated a fine-tuning modulation of svGIA-activated HLMs differentially exerted by the classical macrophage-polarizing cytokines.

Orbital myeloid sarcoma (chloroma): Report of 2 cases and literature review.

PURPOSE: Myeloid sarcoma (MS) of the orbit is an uncommon condition in occurring in children, generally coupled to myeloproliferative neoplasms. OBSERVATIONS: We describe two rare cases of orbital MS in young boys with aggressive local symptoms but without evidence of acute myeloid leukemia (AML), both patients underwent orbitotomy for gross-tumor resection and biopsy. At follow up, there was no evidence of recurrence nor evolution of the myeloproliferative neoplasms clinically and by radiological and laboratory work-up. We also provide a detailed description of the magnetic resonance imaging presentation, with an extensive pathological analysis correlation. CONCLUSIONS AND IMPORTANCE: A comprehensive revision of the literature on isolated orbital MS was carried out with particular emphasis on clues for differential diagnosis and treatment options, stressing the need to consider MS even in the absence of sign and symptoms of an underlying myeloproliferative disorders.

Erratum: Epigenetics of oral and oropharyngeal cancers (Review).

[This corrects the article DOI: 10.3892/br.2018.1136.].