Background: Mucosal addressin cell adhesion molecule-1 (MAdCAM-1), a member of the immunoglobulin superfamily, is essential for gut-specific homing of leukocytes; however, it has not been well characterized in rhesus macaques.

Aims: To obtain the complete nucleotide sequence of rhesus macaque MAdCAM-1 cDNA and determine its distribution in gut-associated lymphoid tissues (GALT) and its alteration in duodenal mucosa after simian/human immunodeficiency virus (SHIV) infection.

Methods: MAdCAM-1 cDNA was cloned from the colon mucosa of a rhesus macaque by 3'- and 5'-RACE. The distribution and abundance of MAdCAM-1 mRNA in the GALT were examined by nested and real-time RT-PCR. The alterations of MAdCAM-1 mRNA levels in SHIV-infected duodenal mucosa were determined by real-time RT-PCR.

Results: The nucleotide sequence of rhesus macaque MAdCAM-1 cDNA (1,503 bp nucleotides) including the 5'- and 3'-untranslated regions was obtained. The coding region (1,086 bp) showed 87.56% and the Ig-like domain 1, 2 and TM + cytoplasmic domains showed >93% nucleotide sequence identity to that of humans. Like humans, rhesus macaques lacked MAdCAM-1 IgA1-like domain, which could be a common feature for all primates appeared later during vertebrate evolution. Two species of MAdCAM-1 mRNA were detected and high-level transcripts were observed primarily in the GALT. The full-length MAdCAM-1 expressed in vitro could bind to human α4β7. MAdCAM-1 mRNA levels were statistically significantly reduced in SHIV-infected duodenal mucosa.

Conclusions: These data provided a basis for using rhesus macaques in pathological and therapeutic studies on leukocyte homing related diseases such as inflammatory bowel disease and HIV/AIDS.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-014-3209-0DOI Listing

Publication Analysis

Top Keywords

madcam-1 mrna
16
rhesus macaques
12
nucleotide sequence
12
rhesus macaque
12
madcam-1 cdna
12
madcam-1
10
mucosal addressin
8
addressin cell
8
cell adhesion
8
adhesion molecule-1
8

Similar Publications

Background: Vedolizumab, an antibody blocking integrin α4β7, is a safe and effective therapy for Crohn's disease and ulcerative colitis. Blocking α4β7 from binding its cognate addressin MAdCAM-1 on intestinal blood vessel endothelial cells prevents T cells from migrating to the gut mucosa in animal models. However, data supporting this mechanism of action in humans is limited.

View Article and Find Full Text PDF
Article Synopsis
  • Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) levels are elevated in the colonic mucosa of ulcerative colitis (UC) patients, particularly during inflammation, and have previously been linked to disease severity.
  • A study involving 80 UC patients in remission found that higher MAdCAM-1 expression was correlated with those who later experienced a relapse, suggesting it could be a predictive marker.
  • The research indicates that MAdCAM-1 expression not only reflects mucosal inflammation but also serves as a potential indicator for relapse and treatment effectiveness in UC.
View Article and Find Full Text PDF

Successful treatment of inflammatory bowel disease (IBD) with the anti-integrin αβ mAb vedolizumab suggests that interaction of this integrin with addressin mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is central to IBD pathogenesis. Although this was presumed to be due to an inhibition of lymphocyte trafficking to the gut, as has been observed in animal models, we report no depletion of CD4 T cells from the colonic mucosa as a consequence of vedolizumab treatment in humans, regardless of efficacy. Likewise, no upregulation of alternative trafficking mechanisms was observed as a consequence of therapy to suggest that this homeostasis is maintained in patients by a mechanistic escape from inhibition.

View Article and Find Full Text PDF

Background And Aim: The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes myeloperoxidase reactivity in Crohn's disease-like ileitis.

View Article and Find Full Text PDF

Seeding of leukocytes to developing lymphoid tissues in embryonic and early postnatal age and to the mucosa throughout adulthood depends on the interaction between endothelial MAdCAM-1 addressin and its cognate ligand α4β7 integrin. Nkx2-3 as a transcriptional regulator of MAdCAM-1 controls vascular patterning in visceral lymphoid tissues in mice, and has been identified as a susceptibility factor for inflammatory bowel diseases in humans, associated with lymphoid neogenesis in the inflamed intestines. The role of Nkx2-3 in the organogenesis of the solitary intestinal lymphoid tissues (SILTs) involving type 3 innate lymphoid cells (ILC3) is still unknown.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!