Distribution and activation of eosinophils in inflammatory bowel disease using an improved immunohistochemical technique

Abstract

Eosinophils are a recognized feature of inflammatory bowel disease (IBD), but their tissue distribution and functional importance in Crohn's disease (CD) and ulcerative colitis (UC) remain obscure. This study describes an improved immunohistochemical protocol to identify eosinophils in full thickness bowel wall specimens of IBD (n=40) and their in situ relationships with the chemoattractants eotaxin and RANTES. Eosinophils were identified using immunohistochemistry with a combination of monoclonal antibodies (EG1+EG2+MBP), an ultrasensitive technique superior to other methodologies, and their tissue distributions were related to those for eotaxin, RANTES, mast cells and neutrophils. Increased numbers of eosinophils (up to 400 cells/mm(2)) were observed in active, fulminant inflammation in both CD and UC, this being related to the severity of inflammation and not the diagnosis of the two disorders. The chemoattractants eotaxin (CCL11) and RANTES (CCL5) were upregulated in IBD tissues showing eosinophilia. Neutrophils and mast cells were commonly associated with eosinophil accumulations. Eosinophil numbers and their in situ activation are increased in active rather than chronic IBD. The observations strongly suggest a pivotal role for the eosinophil and its potent mediators in many pathophysiological symptoms of CD and UC, where it represents the major proportion of all granulocytic cells in active inflammatory bowel disease.

Immunopathogenesis of Experimental Ulcerative Colitis Is Mediated by Eosinophil Peroxidase

“…During inflammatory responses, IL-13 has been shown to regulate an array of eosinophil-sensitive functions including eotaxin production and eosinophil recruitment and survival (33)(34)(35)(36). Elevated levels of eotaxin have also been observed in serum and biopsy samples from patients with UC consistent with a role for eotaxin in eosinophil accumulation into the GI tract during UC (6,11,37,38). Using eotaxin Ϫ/Ϫ mice, we demonstrate an important role for eotaxin in the recruitment of eosinophils into the colon during experimental UC.…”

“…Recently, there has been increasing interest in the involvement of eosinophils in the pathogenesis of UC (6). Elevated levels of eosinophils have been observed in colonic biopsy samples from UC patients and increased numbers of this cell have been shown to correlate with morphological changes to the GI tract, disease severity, and gastrointestinal dysfunction (7)(8)(9)(10).…”

Tissue Eosinophilia in a Mouse Model of Colitis Is Highly Dependent on TLR2 and Independent of Mast Cells

“…Eosinophils have been observed in the intestinal tissues of patients with Crohn's disease and ulcerative co- litis as well as in the airways of asthmatics, but their contribution to the observed pathology of these diseases remains uncertain. 14,52 Eosinophil accumulation in the mucosa is a common feature observed during DSS-induced colitis in mice. 16,17 We and others have previously shown that TLR2 signaling in response to the commensal microflora is important in limiting mucosal injury during DSS colitis.…”

The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract

“…Eosinophils are not histological landmarks in either Crohn's disease or in ulcerative colitis, though they do represent the major portion of all granulocytic cells in active or fulminant IBD, independent of the type of disorder. Moreover, IBD patients with a significant tissue eosinophilia demonstrate increased expression of eotaxin and RANTES (95). It has also been demonstrated that flare-ups are correlated with an elevated faecal excretion of eosinophil cationic protein (96).…”

“…Interestingly, a quantitative assessment of the eosinophils in the mucosa of patients with ulcerative colitis showed that patients having a benign course of the disease and a good response to treatment have significantly higher eosinophil levels in the mucosa than do those patients who have an aggressive form of the disease and fail to respond to medical treatment (97). All these observations suggest that the eosinophils and their mediators are actively involved in the inflammatory process of both Crohn's disease and ulcerative colitis Their role is certainly more than that of an Ôinnocent bystanderÕ (95). However, Crohn's disease bears many features of a T H1 type inflammation, whereas ulcerative colitis is closer aligned with allergies (98).…”