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.
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http://dx.doi.org/10.1007/s10620-014-3209-0 | DOI Listing |
Inflamm Bowel Dis
May 2024
Center for Translational Research, Benaroya Research Institute, Seattle, WA, USA.
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 PDFJ Crohns Colitis
May 2023
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, Japan 602-8566.
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 PDFJ Gastroenterol Hepatol
November 2021
Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
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 PDFFront Immunol
July 2020
Department of Immunology and Biotechnology, Clinical Center, University of Pécs, Pécs, Hungary.
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.
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