Neutrophil Motility in Crohn’s Disease

Curran, Francis T.; Keighley, M. R. B.

doi:10.1159/000200680

Cited by 4 publications

(2 citation statements)

References 24 publications

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“…Experimental colitis has been shown to alter neutrophil function in the peripheral circulation (6), with enhancement of superoxide generation, leukotriene B 4 synthesis, and phagocytosis and inhibition of chemotaxis (6). In patients with inflammatory bowel diseases, peripheral neutrophil functions are altered (8,13,16), and it is thought that these alterations may lead to nonspecific injury. In patients with shigellosis there is extensive colitis with a predominant neutrophil infiltration (14) so that, as in patients with inflammatory bowel disease, neutrophil activation could have a role in precipitating nonspecific injury in patients with shigellosis.…”

Section: Discussionmentioning

confidence: 99%

“…Other inflammatory conditions of the gut, such as ulcerative colitis and Crohn's disease, are associated with alterations in peripheral blood neutrophil function (8,13,16) which are thought to contribute to intestinal and extraintestinal nonspecific injury. Neutrophil function has not been measured in patients with shigellosis, particularly that caused by S. dysenteriae type 1, in which there is extensive colitis.…”

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Peripheral blood neutrophil responses in children with shigellosis

Azim

Islam

Halder

et al. 1995

Clin Diagn Lab Immunol

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Alterations in peripheral blood neutrophil function are known to occur in patients with colitis and may have a role in precipitating nonspecific tissue injury. It is not known whether neutrophil function is altered in patients with Shigella dysenteriae type 1 infection, during which there is extensive colitis and which may be associated with life-threatening complications in young children. Three aspects of peripheral blood neutrophil function, polarization, attachment to yeast particles, and locomotion, were therefore studied in 111 children with S. dysenteriae type 1 infection and 57 children without any infection. All children were aged 12 to 60 months. Of the children with S. dysenteriae type 1 infection, 42 had leukemoid reaction, hemolytic-uremic syndrome, or septicemia (complicated shigellosis), while the others did not (uncomplicated shigellosis). Polarization and locomotion in the absence of chemoattractants and in response to N-formylmethionyl-leucylphenylalanine (FMLP) and the lipopolysaccharide (LPS) of S. dysenteriae type 1 were determined. Attachment to unopsonized and opsonized yeast particles was also determined. Children with shigellosis (uncomplicated or complicated) had more polarized neutrophils with and without chemoattractants than uninfected children (P < 0.05). Children with complicated shigellosis had more polarized neutrophils with FMLP at 10 ؊7 and 10 ؊6 M (P < 0.05) and with LPS than children with uncomplicated shigellosis (P < 0.05). At 3 to 5 days after enrollment, the numbers of polarized neutrophils with 10 ؊8 , 10 ؊6 , and 10 ؊5 M FMLP declined in children with uncomplicated shigellosis but not in those with complicated shigellosis. Attachment to yeast particles was similar in all three groups of children. Locomotion was inhibited by LPS in children with shigellosis (P < 0.05), whether it was uncomplicated or complicated, compared with locomotion in uninfected children. Finally, neutrophil polarization in uninfected children was negatively influenced by nutritional status. Thus, poorly nourished uninfected children had more polarized neutrophils with FMLP at 10 ؊9 M (P ‫؍‬ 0.020) and 10 ؊5 M (P ‫؍‬ 0.043) than their better-nourished counterparts. In summary, altered neutrophil responses are associated with both uncomplicated and complicated shigellosis.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Peripheral blood neutrophil responses in children with shigellosis

Azim

Islam

Halder

et al. 1995

Clin Diagn Lab Immunol

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Alterations in rat peripheral blood neutrophil function as a consequence of colitis

Carter

Wallace

1995

Digest Dis Sci

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Altered peripheral neutrophil function is a feature of IBD that may contribute to the chronicity and extragastrointestinal manifestations of this disease, but clinical evidence for such alterations is confounded by variations in patient characteristics, disease onset, and use of therapeutics that can influence neutrophil function. The use of a rat model of colitis has permitted us to characterize, in a controlled manner, the causal relationship between colitis and altered peripheral neutrophil function. At various times after induction of colitis with trinitrobenzene sulfonic acid (TNBS), peripheral neutrophils were isolated and assays of phagocytosis, chemotaxis, leukotriene B4 (LTB4) synthesis, and superoxide production were performed using a variety of stimuli. Circulating neutrophil numbers increased about fourfold within 12 hr of TNBS administration and returned to normal levels over the following two weeks. LTB4 synthesis in response to calcium ionophore decreased at 12 hr after induction of colitis, then returned to control levels. The chemotactic responses of peripheral neutrophils to LTB4 and FMLP in vitro and to LTB4 and IL-8 in vivo were profoundly suppressed through the two-week study period. Phagocytosis of nitroblue tetrazolium was significantly enhanced (ca. threefold) at 12 hr after induction of colitis and remained elevated throughout the study period. Superoxide production was also significantly elevated in the early phase of colitis (by ca. fourfold), but was not different from control levels at seven and 14 days. These results demonstrate that colonic inflammation profoundly influences peripheral blood neutrophil function, although the direction and magnitude of the alteration varied among the various functions assessed. The prolonged depression of chemotactic activity may represent a physiological reaction to limit the inflammatory response.

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Crohn’s as an immune deficiency: from apparent paradox to evolving paradigm

Vinh

Behr²

2013

Expert Review of Clinical Immunology

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Crohn's disease is often considered an autoimmune condition, based on the observations of a histopathological inflammatory process in the absence of identifiable causal microorganism(s) and that immune-modulating therapeutics result in diminished host-directed inflammatory pathology. However, the evidence for a self-targeted immune response is unproven; thus, the instigating and perpetuating forces that drive this chronic inflammation remain unknown. In recent years, a convergence of findings from different fields of investigation has led to a new paradigm, where Crohn's disease appears to be the consequence of an intrinsic innate immune deficiency. While genomic/postgenomic studies and functional immunologic investigations offer a common perspective, critical details of the processes involved require further elaboration. In this review, we place this new model in the context of the emerging literature on non-HIV immune deficiencies, to compare and contrast what is known about proven intrinsic (primary) immune deficiencies to the nascent understanding of Crohn's disease. We then re-evaluate postgenomic research, looking at the functional importance of Crohn's disease-associated mutations and polymorphisms, to delineate points of consensus and issues requiring further study. We ask whether the immunologic profile can guide predictions as to which microbial triggers could exploit these defects and thereby initiate and/or perpetuate chronic enteritis. Finally, we outline potential clinical implications of this model, from immunologic assessment of patients to the selection of therapeutic interventions.

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Neutrophil Motility in Crohn’s Disease

Cited by 4 publications

References 24 publications

Peripheral blood neutrophil responses in children with shigellosis

Peripheral blood neutrophil responses in children with shigellosis

Alterations in rat peripheral blood neutrophil function as a consequence of colitis

Crohn’s as an immune deficiency: from apparent paradox to evolving paradigm

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