<p>Pro-inflammatory agents released by pathogens, dying host cells, and neutrophils act synergistically to destroy host tissues: a working hypothesis</p>

Abstract

We postulate that the extensive cell and tissue damage inflicted by many infectious, inflammatory and post-inflammatory episodes is an enled result of a synergism among the invading microbial agents, host neutrophils and dead and dying cells in the nidus. Microbial toxins and other metabolites along with the plethora of pro-inflammatory agents released from activated neutrophils massively recruited to the infectious sites and high levels of cationic histones, other cationic peptides, proteinases and Th1 cytokines released from activated polymorphonuclear neutrophils (PMNs) and from necrotized tissues may act in concert (synergism) to bring about cell killing and tissue destruction. Multiple, diverse interactions among the many potential pro-inflammatory moieties have been described in these complex lesions. Such infections are often seen in the skin and aerodigestive tract where the tissue is exposed to the environment, but can occur in any tissue. Commonly, the tissue-destructive infections are caused by group A streptococci, pneumococci, Staphylococcus aureus, meningococci, Escherichia coli and Shigella, although many other microbial species are seen on occasion. All these microbial agents are characterized by their ability to recruit large numbers of PMNs. Given the complex nature of the disease process, it is proposed that, to treat these multifactorial disorders, a “cocktail” of anti-inflammatory agents combined with non-bacteriolytic antibiotics and measures to counteract the critical toxic role of cationic moieties might prove more effective than a strategy based on attacking the bacteria alone.

Roles of CD38 in the Immune Response to Infection

“…Pathogenic bacteria are causative agents for a wide spectrum of infectious diseases. Bacterial infection causes tissue damage through different mechanisms, including the killing of infected host cells, the secretion of toxins and the induction of an exacerbated inflammatory response [21]. In vivo studies demonstrated that CD38 deficiency in mice conferred increased susceptibility to infection by several bacteria, namely Listeria monocytogenes (L. monocytogenes) [22], Mycobacterium avium (M. avium) [23] and Streptococcus pneumoniae (S. pneumoniae) [24,25], and the parasite Entamoeba histolytica (E. histolytica) [26].…”

To Trap a Pathogen: Neutrophil Extracellular Traps and Their Role in Mucosal Epithelial and Skin Diseases

“…UC and CD share some risk factors, such as age, smoking habits, appendicitis, autoimmune diseases, diet, lifestyle and genetics [33]. The NOD2 gene has been associated with IBD, whose genetic variants are associated with increased susceptibility to the development of CD [34].…”

“…UC is an inflammatory bowel disease that occurs gradually or suddenly in the digestive tract; it damages the lining of the colon and rectum, and it affects the mucosa; it is characterized by the presence of a granular mucosa, superficial ulcers, pseudopolyps, diarrhea, abdominal cramps, fever and fatigue, which can cause friability of the mucosa and bleeding from the intestine [33,36]. With regard to CD, the signs are similar; however, the pathology leads to the development of aphthoid ulcers, fistulas, fissures and stenosis [37].…”

A Novel Hypothetical Approach to Explain the Mechanisms of Pathogenicity of Rheumatic Arthritis

“…These include reactive oxygen and nitrogen species, cationic proteinases, and the membrane-damaging phospholipases and lysophosphatides, 22 – 36 besides the toxic products released by dying cells. 37 It is also of great interest to note that the mechanisms by which PMNs and macrophages destroy tissues are very similar to those mediated by group A haemolytic streptococci. 38 …”