Differential lamina propria cell migration via basement membrane pores of inflammatory bowel disease mucosa

McAlindon, Mark E.; Gray, Trevor; Galvin, A; Sewell, H. F.; Podolsky, Daniel K.; Mahida, Yashwant R.

doi:10.1016/s0016-5085(98)70255-0

Cited by 39 publications

(32 citation statements)

References 23 publications

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“…This is in accordance with previous findings in animal models, 8 in human subjects with colorectal cancer 10 and with electron microscopy data that indicate that the permeability of BMs is altered in pathological conditions. 25 Alternatively, the production of immune-inhibitory cytokines, such as FAS-L, IL-10 or TGF-b may also explain the observed discrepancies in leukocyte infiltration. [26][27][28][29] Regarding the question as to which arm of the immune systems plays the most significant role in the antitumor effect, it is generally believed that the activation of tumor-specific, cytotoxic T cells plays a more prominent role than the leukocytes involved in innate immunity (eg NK cells).…”

Section: Discussionmentioning

confidence: 99%

Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis

Menon

Rhijn

Morreau

et al. 2004

Laboratory Investigation

199

172

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The efficacy of tumor cell-immune cell interactions depends on a number of factors, for example, the expression of HLA-I on tumor cells, the type of immune cell, the accessibility of tumor cells for immune cells and the expression of immunogenic epitopes. We assessed infiltration of CD4 þ , CD8 þ , CD56 þ and CD57 þ cells in the tumor epithelium, tumor stroma and advancing tumor margin of 93 colorectal carcinomas and correlated this to clinicopathological parameters, the expression of HLA-A and HLA-B/C on tumor cells, the presence of a basal membrane (BM)-like structure surrounding tumor nodules and the presence of microsatellite instability/ mutator phenotype (absent MLH-1 expression). The median intraepithelial CD4 þ , CD8 þ , CD56 þ and CD57 þ cell infiltrations were 3, 23, 0 and 0 cells/mm 2 tumor, respectively. HLA-A/BC expression by tumor cells was normal in 28/43%, heterogeneous in 59/48% and absent in 13/9% of the cases. A BM-like structure surrounding the tumor nodules was absent, present and thick in 47, 38 and 15% of the cases. Six cases lost MLH1 expression. There was a positive correlation between leukocyte infiltration in the three compartments for CD4 þ , CD8 þ , CD56 þ (partly) and CD57 þ (all Po0.05) cell infiltration. Intraepithelial CD8 þ cell infiltration inversely correlated with HLA-A (P ¼ 0.04) and HLA-B/C expression (P ¼ 0.04). Intraepithelial CD57 þ cell infiltration inversely correlated with HLA-B/C expression (P ¼ 0.04). Moreover, intraepithelial infiltration of CD8 þ and CD57 þ cells was inversely correlated to the presence of a BM-like structure (P ¼ 0.003 and 0.04, respectively). Uni-and multivariate analyses showed that a lower tumor stage (P ¼ 0.004) and marked infiltration of CD8 þ (P ¼ 0.04) and CD57 þ cells (P ¼ 0.05) at the advancing tumor margin were independent prognostic factors for a longer diseasefree survival. Loss of MLH1 expression was correlated with a significantly higher intraepithelial CD8 þ and CD57 þ cell infiltration. We conclude that infiltration of CD8 þ and CD57 þ cells are important prognostic factors in colorectal cancer. However, their interaction with tumor cells is inversely correlated to the presence of HLA-I on tumor cells and a thick BM-like structure around tumor islets. Our data indicate that NK cells might play an important role in the immune surveillance in colorectal cancer patients.

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Section: Discussionmentioning

confidence: 99%

Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis

Menon

Rhijn

Morreau

et al. 2004

Laboratory Investigation

199

172

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“…It is currently unclear whether the DC (or precursors of DC) migrate out of the biopsy through pores in the basement membrane, as occurs for other leukocytes in similar culture systems (18), or whether they exit in the opposite direction as if migrating to draining lymphoid tissue (30). After 24 h in culture these walkout DC express uniformly high levels of maturation-dependent markers.…”

Section: Discussionmentioning

confidence: 99%

Migration and Maturation of Human Colonic Dendritic Cells

Bell

Rigby

English

et al. 2001

The Journal of Immunology

152

143

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Dendritic cells (DC) in the colon may regulate intestinal immunity but remain poorly characterized. In this study a CD11c+HLA-DR+lin− (CD3−CD14−CD16−CD19−CD34−) population has been identified by flow cytometry in cells obtained by rapid collagenase digestion of human colonic and rectal biopsies. These day 0 (d0) CD11c+HLA-DR+lin− cells comprised ∼0.6% of the mononuclear cells obtained from the lamina propria, were endocytically active, and had the phenotype of immature DC; they were CD40+ and expressed low levels of CD83 and CD86, but little or no CD80 or CD25. Similar d0 DC populations were isolated from the colonic mucosa of healthy controls and from both inflamed and noninflamed tissue from patients with Crohn’s disease. The lamina propria also contained a population of cells capable of migrating out of biopsies during an overnight culture and differentiating into mature DC with lower levels of endocytic activity and high cell surface expression of CD40, CD80, CD86, CD83, and CD25. This mature DC population was a potent stimulator of an allogeneic mixed leukocyte (MLR). Overnight culture of cells isolated by enzymatic digestion on d0 yielded DC with a phenotype intermediate between that of the d0 cells and that of the cells migrating out overnight. Overnight culture of colonic cells in which DC and HLA-DR+lin+ cells were differentially labeled with FITC-dextran suggested that some of the maturing DC might differentiate from HLA-DR+lin+ progenitors. This study presents the first analysis of the phenotype, maturational status, and migratory activity of human gut DC.

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“…Recently, a less elaborate technique for the isolation of lamina propria mononuclear cells, which does not require the use of collagenase, has been described (92)(93)(94). This method is based on the capacity of large numbers of lamina propria cells to migrate via distinct pores in the basement membrane, following the loss of epithelial cells.…”

Section: Studies On Isolated Intestinal Macrophagesmentioning

confidence: 99%

“…Some may be lost into the lumen from the ulcerated mucosal surface (92,93), some may migrate out of the mucosa via lymphatic channels to mesenteric lymph nodes, likely as dendritic cells (45,46,164,165).…”

Section: Miscellaneousmentioning

confidence: 99%

The key role of macrophages in the immunopathogenesis of inflammatory bowel disease

Mahida

2007

Inflamm Bowel Dis

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Macrophages are important in the host's immunological and inflammatory responses. There is a large population of these cells in the normal intestinal mucosa where they represent the major antigen presenting cell population capable of determining the type of T cell responses that develop to luminal antigens. Studies suggest that the normal intestinal macrophages cannot be easily induced to mediate acute inflammatory responses. In active inflammatory bowel disease there is an increase in the mucosal macrophage population, derived from circulating monocytes. These recruited macrophages are phenotypically different from the resident population of cells and play a major role in mediating the chronic mucosal inflammation seen in patients with ulcerative colitis and Crohn's disease. They secrete many cytokines that are important in the pro‐inflammatory responses, such as interleukin (IL)‐1, IL‐6, IL‐8, IL‐12, IL‐18, and tumor necrosis factor‐α. They also release reactive metabolites of oxygen and nitrogen and proteases that degrade the extracellular matrix. Macrophages also appear to be important during resolution of inflammation and repair of the intestinal mucosa that occurs during disease remission.

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Differential lamina propria cell migration via basement membrane pores of inflammatory bowel disease mucosa

Cited by 39 publications

References 23 publications

Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis

Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis

Migration and Maturation of Human Colonic Dendritic Cells

The key role of macrophages in the immunopathogenesis of inflammatory bowel disease

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