Bacteria and Neutrophils
Abnormal response to commensal bacteria?
Here's another angle: chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients may be having an abnormal response to bacteria which normally ("commensally") inhabit the prostate.
Recently a discussion arose on the prostatitis newsgroup about the way the immune systems of men with severe cystic acne reacted abnormally to the ubiquitous skin bacterium P.acnes. Could this be relevant in CP/CPPS/chronic prostatitis? Could our prostates be reacting abnormally to commensal bacteria? It's an idea worth exploring, especially since antibiotics can cause temporary improvements in many men (assuming the antibiotics are not helping for other reasons.)
Tests have shown that about one third of asymptomatic men have bacteria
living peacefully, apparently, in their prostates. But if, due to impaired
neutrophil function, your immune system responds abnormally to these
- bacteria which are almost impossible to eradicate permanently - you
may experience chronic inflammation. So, the mechanisms involved in
(especially impaired neutrophil function) may be instrumental in
CP/CPPS too. This news article is interesting in this regard:
Neutrophil impairment proposed as cause of Crohn's disease
WESTPORT, Jul 11 2000 (Reuters Health) - While current theories of the pathogenesis of Crohn's disease suggest a hyperactive immune response, two researchers from Missouri propose instead that impaired mucosal neutrophil function might underlie the disease.
In the June issue of Digestive Diseases and Sciences, Drs. Joshua R. Korzenik and Brian K. Dieckgraefe, from Washington University School of Medicine, in St. Louis, propose that at least some cases of Crohn's disease "result from an interaction of environmental and genetic influences leading to impaired mucosal neutrophil function, resulting in a failure to effectively clear intramucosal microbes effectively."
The authors point out that chronic granulomatous disease, glycogen storage disease Ib, leukocyte adhesion deficiency, Chediak-Higashi syndrome, Turner's syndrome, and congenital, cyclic and autoimmune neutropenias can all present with Crohn's disease or a Crohn's disease-like phenotype. "The unifying feature of these diverse diseases is that each shares a distinct deficiency in quantitative or qualitative neutrophil function," they point out. "These syndromes provide strong evidence that varied functional neutrophil deficiencies can result in a common intestinal phenotype of [Crohn's disease]."
Defects in neutrophil function in Crohn's patients have long been recognized, according to the researchers. These include defects in migration or chemotaxis, superoxide generation, phagocytosis, and microbial killing.
"Inherent neutrophil dysfunction alone does not explain [Crohn's disease]," they admit. But, they argue, impairment of neutrophil function might be worsened in the presence of certain bacteria or bacterial products. Such a process occurs in periodontal disease, they say. "A discrete group of bacteria associated with periodontitis can penetrate gingival epithelium and impede effective clearance by inducing neutrophil functional impairment through elaboration of leukotoxins and other poorly understood mechanisms," they write. "A similar pathogenesis may be functioning in [Crohn's disease]."
The authors comment further that "twentieth century" risk factors for Crohn's disease, including nicotine and nonsteroidal anti-inflammatory drugs, also have detrimental effects on neutrophil function.
With neutrophil function impaired by genetic and environmental influences, the neutrophil response to microbial stimuli is inadequate, and a "compensatory increase and activation of downstream elements of the immune cascade" results, the researchers speculate. They conclude. "Validation of this theory would...yield additional treatment options for the future." ( From Dig Dis Sci 2000;45:1121-1129. )
Here's some relevant recent science:
Neutrophils are among the first cells to arrive at the scene of an infection and are important contributors to the acute inflammatory response (see excellent illustration). As the neutrophil rolls along the blood-vessel wall, the L-selectin on its surface binds to carbohydrate structures such as sialyl-Lewisx on the adhesion molecules on the vascular endothelium, and its progress is eventually halted. As the neutrophil becomes activated, it replaces L-selectin with other cell-surface adhesion molecules, such as integrins. These molecules bind E-selectin, which is present on the blood-vessel wall as a result of the influence of inflammatory mediators such as bacterial lipopolysaccharides and the cytokines interleukin-1 and tumor necrosis factor (alpha). The activated neutrophil then enters the tissues, where it is attracted to the infection site by a number of chemoattractants. The neutrophil can then phagocytose and destroy the C3b-coated bacteria.
The New England Journal of Medicine -- July 6, 2000 -- Vol. 343, No.
1 Advances in Immunology: The Immune System, Peter J. Delves, Ivan M.