Cloning and characterization of the bovine polymeric immunoglobulin receptor-encoding cDNA
ABSTRACT Trans-epithelial transport of polymeric immunoglobulins (pIg) into mucosal and glandular secretions is carried out by the pIg receptor (pIgR). Therefore, expression of the pIgR gene in epithelial cells of mucosal and glandular tissues is an absolute requirement for achieving mucosal immunity. We report the cloning and characterization of the bovine pIgR cDNA. Three overlapping cDNA clones with a total length of 3608 bp yielded an open reading frame encoding a 757-amino-acid (aa) transmembrane (TM) glycoprotein. Although polymorphism was found in two separate clones, Northern blot analysis showed a single pIgR mRNA (approx. 3.8 kb) to be present in the mammary gland, liver, lung, kidney and intestine of a lactating cow. There was no detectable expression of pIgR in the spleen of the same animal. Comparison of the deduced bovine pIgR as sequence with those of rat, mouse, man and rabbit shows that this receptor is highly conserved both in aa sequence and structural organization. The degree of conservation in the TM sequence and the C-terminal cytoplasmic tail, which contains the various signals for intracellular trafficking of the receptor, is 65-73%. We also find a high degree of conservation (61-66%) in the ectoplasmic part of the receptor, known as the secretory component (SC), with an exception for that of the rabbit SC, which is much lower (47%). Among the five Ig-like domains in the SC, the N-terminal domain I, where the primary pIg-binding site is located, showed the highest (72-83%) aa sequence conservation.
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- "PIGR is the gene responsible for trans-epithelial transport of polymeric immunoglobulins such as IgA dimers and IgM pentamers into mucosal and glandular secretions. Its expression is essential for achieving mucosal immunity (Verbeet et al., 1995). Indeed, evidence demonstrated that PIGR knockout mice became more susceptible to Mycobacteria bovis bacillus Calmette-Guerin (BCG) infection (Tjarnlund et al., 2006). "
ABSTRACT: Understanding mechanisms of resistance to gastrointestinal nematodes is important in developing effective and sustainable control programs. A resource population of Angus cattle consisting of approximately 600 animals with complete pedigree records has been developed. The majority of these animals were completely characterized for their resistance to natural challenge by gastrointestinal nematodes. As the first step towards understanding the molecular basis of disease resistance, we investigated expression profiles of 17 cytokines, cytokine receptors, and chemokines using real-time RT-PCR in animals demonstrating resistance or susceptibility to pasture challenge. The animals exposed to natural infection for approximately 6 months were treated to remove existing parasites and then experimentally challenged with both Ostertagia ostertagi and Cooperia oncophora. The mRNA expression profiles of these genes in abomasal and mesenteric lymph nodes (ALN, MLN), fundic and pyloric abomasa (FA, PA), and small intestine (SI) were compared between resistant and susceptible animals. Resistant heifers exhibited elevated expression of inflammatory cytokines such as TNFalpha, IL-1beta, and MIP-1alpha in fundic and pyloric abomasa 7 days post infection. Expression levels of IL-10, polymeric immunoglobullin receptor gene (PIGR), and WSX-1 were also 2.7-19.9-folds higher in resistant than susceptible heifers in these tissues. No difference in expression of CXCL6, CXCL10, IFN-gamma, IL-2, IL-4, IL-6, IL-8, IL-12 p40, IL-13, IL-15 and IL-18 was observed between the two groups. The expression of MIP-1alpha, IL-6, and IL-10 was also elevated in small intestines in resistant animals. In contrast, little difference in expression of these genes was detected between resistant and susceptible groups in the draining lymph nodes. These data indicate that resistant animals can better maintain inflammatory responses at the site of infection, suggesting a possible novel mechanism of resistance.Veterinary Parasitology 05/2007; 145(1-2):100-7. DOI:10.1016/j.vetpar.2006.11.015 · 2.55 Impact Factor
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ABSTRACT: The mucosal surfaces lining the gastrointestinal, respiratory and genitourinary tracts are continuously bombarded by potentially infectious agents such as bacteria, viruses, fungi, and parasites, in addition to soluble dietary and environmental substances. The first line of specific immunological defense against these environmental antigens is secretory IgA (SIgA) (Brandtzaeg et al., 1997; Lamm, 1997), which is produced by selective transport of polymeric IgA (pIgA) across epithelial cells lining mucosal surfaces (Kaetzel, 2005; Kaetzel and Mostov, 2005; Norderhaug et al., 1999). The magnitude of this transport process is impressive; it has been estimated that ~3 g of SIgA are transported daily into the intestines of the average adult (Conley and Delacroix, 1987; Mestecky et al., 1986). Transport of polymeric immunoglobulins (IgA and, to a lesser extent, IgM) across mucosal epithelial cells is mediated by a transmembrane glycoprotein called the polymeric immunoglobulin receptor (pIgR).01/1970: pages 43-89;
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ABSTRACT: The main objective of this work was to unequivocally determine the C-terminal sequence of human milk free secretory component (SC). It was found to end at arginine-585, i.e. 33 amino acids downstream from the major heterogeneous C-terminal residue previously identified for colostrum SC. In contrast, our data showed that the C-terminal end of SC was found to be homogeneous. Conflicting assignments, Asp/Gln, a missing Asn-211, Asp/Asn, Glu/Gln were corrected and found to agree with the cDNA sequence. An Ala/Val substitution at position 562 (domain VI) was identified. Its genetic significance is uncertain at present.FEBS Letters 07/1997; 410(2-3):443-6. DOI:10.1016/S0014-5793(97)00629-7 · 3.34 Impact Factor