Histamine as a mediator of cross-talk between human lung mast cells and macrophages.

Histamine, a multifaceted inflammatory mediator released from mast cells and basophils, has long been recognized for its critical role in orchestrating various aspects of allergic responses. Historically, the role of macrophages in allergic disorders has been underestimated compared to other immune cells, such as mast cells, eosinophils, and basophils. These cells are the predominant immune cells in the human lung, both in healthy individuals and patients with asthma.

Differential activation of monocytes and PMNs in orofacial granulomatosis patients induced by bacterial and non-bacterial stimuli.

Introduction: Orofacial Granulomatosis (OFG) is a rare chronic inflammatory disorder characterized by persistent or recurrent swelling of the lips and oral mucosa, often accompanied by granulomatous inflammation in the orofacial region with limited effective treatment options available. Emerging evidence suggests an immune dysregulation in the development and progression of OFG. Immune cells, including monocytes and neutrophils (PMNs), are involved in autoimmune and inflammatory diseases by releasing pro-inflammatory and immunomodulatory molecules.

The JAK1/JAK2 inhibitor ruxolitinib inhibits mediator release from human basophils and mast cells.

Introduction: The Janus kinase (JAK) family includes four cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) constitutively bound to several cytokine receptors. JAKs phosphorylate downstream signal transducers and activators of transcription (STAT). JAK-STAT5 pathways play a critical role in basophil and mast cell activation.

Innate Immune Cells in Melanoma: Implications for Immunotherapy.

The innate immune system, composed of neutrophils, basophils, eosinophils, myeloid-derived suppressor cells (MDSCs), macrophages, dendritic cells (DCs), mast cells (MCs), and innate lymphoid cells (ILCs), is the first line of defense. Growing evidence demonstrates the crucial role of innate immunity in tumor initiation and progression. Several studies support the idea that innate immunity, through the release of pro- and/or anti-inflammatory cytokines and tumor growth factors, plays a significant role in the pathogenesis, progression, and prognosis of cutaneous malignant melanoma (MM).

Neutrophil extracellular traps and neutrophil-related mediators in human thyroid cancer.

Background: Polymorphonuclear neutrophils (PMNs) are the main effector cells in inflammatory responses and play multiple roles in thyroid cancer (TC). PMNs contain and release a plethora of mediators, including granular enzymes [e.g.

Melanoma-derived soluble mediators modulate neutrophil biological properties and the release of neutrophil extracellular traps.

Polymorphonuclear neutrophils (PMNs) are the main effector cells in the inflammatory response. The significance of PMN infiltration in the tumor microenvironment remains unclear. Metastatic melanoma is the most lethal skin cancer with an increasing incidence over the last few decades.

Thymic stromal lymphopoietin (TSLP) is a substrate for tryptase in patients with mastocytosis.

Mastocytosis is a heterogeneous disease associated to uncontrolled proliferation and increased density of mast cells in different organs. This clonal disorder is related to gain-of-function pathogenic variants of the c-kit gene that encodes for KIT (CD117) expressed on mast cell membrane. Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, which plays a key role in allergic disorders and several cancers.

SARS-CoV-2 Spike Protein Activates Human Lung Macrophages.

COVID-19 is a viral disease caused by SARS-CoV-2. This disease is characterized primarily, but not exclusively, by respiratory tract inflammation. SARS-CoV-2 infection relies on the binding of spike protein to ACE2 on the host cells.

PD-L1 neutrophils as novel biomarkers for stage IV melanoma patients treated with nivolumab.

Melanoma displays a rising incidence, and the mortality associated with metastatic form remains high. Monoclonal antibodies that block programmed death (PD-1) and PD Ligand 1 (PD-L1) network have revolutionized the history of metastatic disease. PD-L1 is expressed on several immune cells and can be also expressed on human neutrophils (PMNs).

Size-based effects of anthropogenic ultrafine particles on activation of human lung macrophages.

The anthropogenic particulate matter (PM), suspended air dust that can be inhaled by humans and deposited in the lungs, is one of the main pollutants in the industrialized cities atmosphere. Recent studies have shown that PM has adverse effects on respiratory diseases. These effects are mainly due to the ultrafine particles (PM0.

Neutrophil Extracellular Traps, Angiogenesis and Cancer.

Human neutrophils, the most abundant circulating leukocytes, are fundamental components of the host response against different pathogens. Until a few years ago, neutrophils received limited attention in cancer immunology. Recently, it was discovered that both circulating, and tumor-associated, neutrophils possess functional plasticity when exposed to various inflammatory stimuli and in the tumor microenvironment.

Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma.

Neutrophils (PMNs) contain and release a powerful arsenal of mediators, including several granular enzymes, reactive oxygen species (ROS) and neutrophil extracellular traps (NETs). Although airway neutrophilia is associated with severity, poor response to glucocorticoids and exacerbations, the pathophysiological role of neutrophils in asthma remains poorly understood. Twenty-four patients with asthma and 22 healthy controls (HCs) were prospectively recruited.

Neutrophil extracellular traps in cancer.

Beyond their well-known functions in the acute phases of the immune response, neutrophils play important roles in the various phases of tumor initiation and progression, through the release of their stored or newly synthesized mediators. In addition to reactive oxygen species, cytokines, chemokines, granule proteins and lipid mediators, neutrophil extracellular traps (NETs) can also be released upon neutrophil activation. NET formation can be achieved through a cell-death process or in association with the release of mitochondrial DNA from viable neutrophils.

Roles of Immune Cells in Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare genetic disease, characterized by recurrent and unexpected potentially life-threatening mucosal swelling. HAE may be further classified into HAE with C1-inhibitor deficiency (C1-INH-HAE) and HAE with normal C1-INH activity (nlC1-INH-HAE), mostly due to mutations leading to increased vascular permeability. Recent evidence implicates also the innate and adaptive immune responses in several aspects of angioedema pathophysiology.

Vascular endothelial growth factors and angiopoietins as new players in mastocytosis.

Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects.

IL-33 and Superantigenic Activation of Human Lung Mast Cells Induce the Release of Angiogenic and Lymphangiogenic Factors.

Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are strategically located in different compartments of human lung, where they play a role in several inflammatory disorders and cancer. Immunoglobulin superantigens (e.g.

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

In this study we investigated the effects of snake venom Group IA secreted phospholipase A (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-1β, CXCL8 and CCL1 release induced by both LPS and svGIA.

VEGF-A in Cardiomyocytes and Heart Diseases.

The vascular endothelial growth factor (VEGF), a homodimeric vasoactive glycoprotein, is the key mediator of angiogenesis. Angiogenesis, the formation of new blood vessels, is responsible for a wide variety of physio/pathological processes, including cardiovascular diseases (CVD). Cardiomyocytes (CM), the main cell type present in the heart, are the source and target of VEGF-A and express its receptors, VEGFR1 and VEGFR2, on their cell surface.

LPS-mediated neutrophil VEGF-A release is modulated by cannabinoid receptor activation.

Neutrophils (PMNs) are innate immune cells with primary roles in inflammation and in host defense against infections. Both inflammatory and tumor angiogenesis are modulated by a sequential, coordinated production of angiogenic factors such as vascular endothelial growth factors (VEGFs), angiopoietins, hepatocyte growth factor (HGF), and chemokines. These factors are produced by several immune cells, including PMNs.

Anaplastic Thyroid Cancer Cells Induce the Release of Mitochondrial Extracellular DNA Traps by Viable Neutrophils.

Neutrophils are key effector cells that orchestrate inflammatory responses in the tumor microenvironment. Although neutrophil extracellular DNA traps (NETs) entrap and kill pathogens, they also contribute to chronic inflammation and cancer progression. Thyroid cancer (TC) is the most frequently occurring cancer of the endocrine system, accounting for 70% of deaths due to endocrine tumors.

Hereditary angioedema attack: what happens to vasoactive mediators?

Hereditary angioedema is a disabling, life-threatening condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein (C1-INH-HAE) leading to bradykinin accumulation and recurrent episodes of edema attack. Vascular leakage is a complex process sustained by the coordinated production of several permeabilizing factors including vascular endothelial growth factors (VEGFs), angiopoietins (ANGPTs) and phospholipase A enzymes (PLA). We previously reported that patients with C1-INH-HAE in remission have increased plasma levels of VEGFs, ANGPTs and secreted PLA.

Innate effector cells in angiogenesis and lymphangiogenesis.

Angiogenesis and lymphangiogenesis are distinct and complex processes requiring a finely tuned balance between stimulatory and inhibitory signals. During adulthood, angiogenesis and lymphangiogenesis are activated at sites of tumor growth, tissue injury and remodeling, and chronic inflammation. Vascular endothelial growth factors (VEGFs), angiopoietin (ANGPTs) and a multitude of additional signaling molecules play distinct roles in the modulation of angiogenesis/lymphangiogenesis.