Neutrophilic superficial eccrine ductitis: Proposal of a new disease concept

A 3‐year‐old Japanese boy presented with a 3‐month history of itchy erythematous papules on his trunk and forearms, the histologic findings of which were characterized by predominantly neutrophilic inflammation within and around the eccrine sweat ducts and obliteration and disruption of the superficial eccrine sweat ducts. Although the skin disorder had some clinical and histopathologic similarity to miliaria and neutrophilic eccrine hidradenitis, it was ultimately conformed to be neither disorder. Based on this and a case report in the Japanese literature of a 1‐year‐old boy with erythematous eruptions whose clinical and histopathologic findings were similar to those in our case, we propose the skin disorder in our case, referred to as “neutrophilic superficial eccrine ductitis,” as a unique entity.     

The pro-inflammatory role of platelets in cancer

Thrombosis is a frequent issue in cancer patients. Tumor-induced platelet activation and coagulation does not only constitute a significant risk for thrombosis, but also contribute to tumor progression by promoting critical processes such as angiogenesis and metastasis. In addition to their role in hemostasis, platelets are increasingly recognized as regulators of inflammation. By modulating the immune system, platelets regulate several aspects of cancer-associated pathology. Platelets influence the inflammatory response in cancer by affecting the activation status of the endothelium and by recruiting leukocytes to primary and metastatic tumor sites, as well as to distant organs unaffected by tumor growth. Furthermore, platelets participate in the formation of neutrophil extracellular traps, which can promote metastasis, thrombosis, and contribute to organ failure. In this review, we discuss the role of platelets as coordinators of the immune system during malignant disease and the potential of targeting platelets to prevent cancer-associated pathology.     

Apoptosis driven infection

Professional phagocytes like polymorphonuclear neutrophil granulocytes (PMN) and macrophages (MF) kill pathogens as the first line of defense. These cells possess numerous effector mechanisms to eliminate a threat at first contact. However, several microorganisms still manage to evade phagocytic killing, survive and retain infectivity. Some pathogens have developed strategies to silently infect their preferred host phagocytes. The best example of an immune silencing phagocytosis process is the uptake of apoptotic cells. Immune responses are suppressed by the recognition of phosphatidylserine (PS) on the outer leaflet of their plasma membrane. Taking Leishmania major as a prototypic intracellular pathogen, we showed that these organisms can use the apoptotic “eat me” signal PS to silently enter PMN. PS-positive and apoptotic parasites, in an altruistic way, enable the intracellular survival of the viable parasites. Subsequently these pathogens again use PS exposition, now on infected PMN, to silently invade their definitive host cells, the MF. In this review, we will focus on L. major evasion strategies and discuss other pathogens and their use of the apoptotic “eat me” signal PS to establish infection.     

Primed neutrophil infiltrations into multiple organs in child physical abuse cases: A preliminary study

Physical abuse of the elderly induces a massive primed neutrophil infiltration into the lung and liver through chemotaxis by interleukin (IL)-8, similar to cases of traumatic or hemorrhagic shock. Here, we used immunohistochemical analyses to investigate this infiltration in cases of physically abused children. In addition, we examined the expression of neutrophil elastase (NE) as the inflammatory mediator and α1-antitrypsin (AAT) as the elastase inhibitor. The number of neutrophils in the abuse cases was increased significantly in the heart, lung, liver, and kidney, compared with that of control cases. IL-8-positive cells and NE-positive cells in all organs of abuse cases were significantly greater than those in control cases. Large quantities of oxidized AAT, which fails to inactivate NE and results in tissue damage, was detected in the liver of abuse cases. Neutrophil infiltration showed positive correlation with the degree of systemic accumulation of non-fatal injuries caused by repetitive abusive behavior. Although further investigation using more autopsy samples is necessary, results of our preliminary study indicate that massive neutrophil infiltration induced by IL-8 in multiple organs is a new complementary diagnostic indicator of physical abuse in children. Moreover, the demonstration of NE-positive cells and oxidized AAT provides firm evidence of tissue damage.     

Targeting neutrophils in sepsis

Sepsis continues to have a high mortality rate worldwide. The multi-step effects of this syndrome make it difficult to develop a comprehensive understanding of its pathophysiology and to identify a direct treatment. Neutrophils play a major role in controlling infection. Interestingly, the recruitment of these cells to an infection site is markedly reduced in severe sepsis. The systemic activation of Toll-like receptors and high levels of TNF-α and nitric oxide are involved in the reduction of neutrophil recruitment due to down-regulation of CXCR2 in neutrophils. By contrast, CCR2 is expressed in neutrophils after sepsis induction and contributes to their recruitment to organs far from the infection site, which contributes to organ damage. This review provides an overview of the recent advances in the understanding of the role of neutrophils in sepsis, highlighting their potential as a therapeutic target.     

ANCA-associated vasculitis: is there a role for neutrophil apoptosis in autoimmunity?

The primary small vessel systemic vasculitides are disorders that target small blood vessels, inducing vessel wall inflammation, and are associated with the development of antineutrophil cytoplasmic antibodies. Multiple organs are attacked including the lungs and kidneys. Increasing knowledge of pathogenesis suggests that the antibodies activate neutrophils inappropriately, leading to endothelial and vascular damage. Cytokines, such as tumor necrosis factor, can facilitate damage by priming neutrophils and activating endothelial cells. Apoptosis of infiltrating neutrophils is also disrupted by antineutrophil cytoplasmic antibody activation. Removal of these effete cells occurs in a proinflammatory manner, promoting persistent inflammation. The autoimmune response may be promoted by aberrant phagocytosis of apoptotic neutrophils by dendritic cells. Understanding pathogenesis can help to rationalize existing therapies and indicate new approaches to therapy.