Selectins: critical mediators of leukocyte recruitment

Patel, Kamala D.; Cuvelier, Susan L.; Wiehler, Shahina

doi:10.1006/smim.2001.0344

Cited by 182 publications

(125 citation statements)

References 84 publications

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“…L-selectin is believed to have a role in attracting leukocytes to inflammatory sites, in the activation of leukocytes, and in interactions between leukocytes and endothelial cells (Patel et al, 2002;Rosen, 1999). Although the principal ligand contact points of the selectins lie within the lectin domain (Somers et al, 2000), the EGF domain can modulate the binding properties of the lectin domain (Dwir et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Association between the Phe206Leu polymorphism of L-selectin and brucellosis

Rafiei

Hajilooi²,

Shakib

et al. 2006

Journal of Medical Microbiology

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Brucellosis remains a major zoonosis worldwide; therefore, better understanding of its immunology is a priority for the development of new therapeutic and vaccination strategies. Genetic factors appear to have an important role in the pathogenesis of infectious diseases such as brucellosis. Adhesion molecules, such as members of the selectin family, participate in the interaction between leukocytes and the endothelium, as well as in inflammatory cell recruitment. The impact of L-selectin polymorphisms on brucellosis has not so far been investigated. The aim of this study was to assess an L-selectin Phe206Leu (F206L) polymorphism in patients with active brucellosis, and to analyse its possible relationship with disease progression. A case-control association study was carried out on 619 subjects, including 374 patients with brucellosis and 245 age-and sex-matched healthy controls. Genomic DNA was isolated, and amplification of L-selectin genomic regions was performed by PCR incorporating sequence-specific primers (PCR-SSP) to distinguish the genotypes. The frequencies of the F206L polymorphism were studied. A significant difference in F206L polymorphism was found between patients with brucellosis and controls. The 206Leu allele was more frequent in patients than in healthy individuals (36?6 versus 28 %, P=0?003). In addition, there was an association between the presence of the 206Leu allele and a relapse of brucellosis (odds ratio 6?53, 95 % confidence interval 1?5-28?8, P=0?005). The higher frequency of L-selectin genotypes in patients with brucellosis than in control individuals, as well as the association between the 206Leu allele and the occurrence of brucellosis relapse, suggest that the F206L polymorphism could make individuals more vulnerable to brucellosis.

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Section: Discussionmentioning

confidence: 99%

Association between the Phe206Leu polymorphism of L-selectin and brucellosis

Rafiei

Hajilooi²,

Shakib

et al. 2006

Journal of Medical Microbiology

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“…However, many other hematopoietic cells could be involved. Many of these cells express ␤3-integrins and͞or L-selectin and selectin ligands (also P-selectin in the case of platelets) and may use P-and E-selectins expressed by endothelial cells as well as integrins during their trafficking and extravasation (24)(25)(26). Although we certainly would not wish to rule out platelets, mast cells, eosinophils, or other minor leukocyte populations from consideration, obvious candidate cell types for involvement are neutrophils, monocytes͞macrophages, and NK cells.…”

Section: Discussionmentioning

confidence: 99%

Increased primary tumor growth in mice null for β3- or β3/β5-integrins or selectins

Taverna

Moher

Crowley

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Expression of ␣v␤3-or ␣v␤5-integrins and selectins is widespread on blood cells and endothelial cells. Here we report that human tumor cells injected s.c. into mice lacking ␤3-or ␤3͞␤5-integrins or various selectins show enhanced tumor growth compared with growth in control mice. There was increased angiogenesis in mice lacking ␤3-integrins, but no difference in structure of the vessels was observed by histology or by staining for NG2 and smooth muscle actin in pericytes. Bone marrow transplants suggest that the absence of ␤3-integrins on bone marrow-derived host cells contributes to the enhanced tumor growth in ␤3-null mice, although few, if any, bone marrow-derived endothelial cells were found in the tumor vasculature. Tumor growth also was affected by bone marrow-derived cells in mice lacking any one or all three selectins, implicating both leukocyte and endothelial selectins in tumor suppression. Reduced infiltration of macrophages was observed in tumors grown in mice lacking either ␤3-integrins or selectins. These results implicate cells of the innate immune system, macrophages or perhaps natural killer cells, in each case dependent on integrins and selectins, in tumor suppression.tumors ͉ bone marrow transplants ͉ cell adhesion ͉ innate immunity W e have previously investigated the growth and metastasis of transplanted tumors in mice lacking specific celladhesion receptors, namely integrins (1-3) or selectins (4-6).In mice lacking ␣v-integrins (␣v␤3 and ␣v␤5), tumors grow larger; this growth is accompanied by enhanced tumor angiogenesis (2). However, it is unclear whether other factors, such as altered vessel morphology, pericyte recruitment, or altered immune responses in the integrin-deficient mice, may contribute to the enhanced tumor growth.In the case of selectins, we have shown that experimental metastases to the lungs are reduced in mice lacking P-and͞or L-selectins (4-6). This reduction is believed to result from the tumor cells' expression of ligands for selectins such that selectins on host platelets, leukocytes, or endothelial cells can bind these ligands and promote metastatic arrest in the lungs after tail vein injection (7-10). Examination of this hypothesis using a more complete model of metastasis, such as metastasis from a s.c. site, would be desirable.Given these two prior lines of investigation and the questions they raised, we have investigated further the s.c. growth of xenotransplanted tumors in mice lacking various combinations of integrins or selectins. We report here results indicating that both ␤3-integrins and selectins contribute to host responses suppressing tumor growth. In each case, bone marrow (BM)-derived host cells, dependent on integrins or selectins, seem to inhibit tumor growth, and in the absence of these adhesion receptors tumors grow significantly larger. Materials and MethodsMice. All mice were generated in our own laboratory. ␤3-Integrinnull mice (2, 11-12) were intercrossed with mice lacking the Rag2 gene (13) and with mice lacking ␤5-integrin (14) to generate mi...

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“…26 The increase in protein expression may reflect the release of stored P-Selectin from storage granules rather than increased gene expression, as P-Selectin is constitutively produced in the secretory granules of platelets (a-granules) and endothelial cells (Weibel-Palade bodies), but is not expressed on the cell surface until an appropriate stimulus is provided. 14 Given the evidence presented above, it is intriguing to hypothesize that variants in P-Selectin may have a role in renal lupus, but we do not have sufficient power within the UK SLE cohort used for this paper to assess whether the association in P-Selectin is stronger for UK SLE families in which the affected offspring has renal disease.…”

Section: Meta-analysismentioning

confidence: 98%

“…P-Selectin is primarily expressed on the cell membrane of platelets and endothelial cells after cellular activation by molecules such as histamine or thrombin, which cause release of the protein from a-granules (platelets) or Weibel-Palade bodies (endothelial cells). [11][12][13][14] The protein functions as an adhesion molecule for a variety of leukocytes, including neutrophils, monocytes, T cells, eosinophils, basophils, platelets and some malignant cells, 15 thereby bringing to sites of inflammation and into contact with a range of cytokines and chemokines expressed by endothelial cells. There are two receptors for P-Selectin, the major leukocyte receptor, P-selectin glycoprotein ligand 1 (PSGL1), which is the high affinity receptor on both myeloid cells and stimulated T lymphocytes, 16,17 and CD24, which is expressed on a number of cells, including B-lineage cells and T lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Variation in the upstream region of P-Selectin (SELP) is a risk factor for SLE

et al. 2009

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Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Genome-wide linkage studies implicated a region containing the adhesion molecule P-Selectin. This family-based study revealed two regions of association within P-Selectin . The strongest signal, from a 21.4-kb risk haplotype, stretched from the promoter into the first two consensus repeat (CR) regions ( P =8 × 10 −4 ), with a second association from a 14.6-kb protective haplotype covering CR 2–9 ( P =0.0198). The risk haplotype is tagged by the rare C allele of rs3753306, which disrupts the binding site of the trans-activating transcription factor HNF-1 . One other variant (rs3917687) on the risk haplotype was significant after permutation ( P 10000 <1 × 10 −5 ), replicated in independent pseudo case-control analysis and was significant by meta-analysis ( P = 4.37 × 10 −6 ). A third associated variant on the risk haplotype (rs3917657) replicated in 306 US SLE families and was significant in a joint UK-SLE data set after permutation. The protective haplotype is tagged by rs6133 (a non-synonymous variant in CR8 ( P =9.00 × 10 −4 ), which also shows association in the pseudo case-control analysis ( P =1.09 × 10 −3 ) and may contribute to another signal in P-Selectin . We propose that polymorphism in the upstream region may reduce expression of P-Selectin, the mechanism by which this promotes autoimmunity is unknown, although it may reduce the production of regulatory T cells.

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Selectins: critical mediators of leukocyte recruitment

Cited by 182 publications

References 84 publications

Association between the Phe206Leu polymorphism of L-selectin and brucellosis

Association between the Phe206Leu polymorphism of L-selectin and brucellosis

Increased primary tumor growth in mice null for β3- or β3/β5-integrins or selectins

Variation in the upstream region of P-Selectin (SELP) is a risk factor for SLE

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