Regulation and lectin activity of the human neutrophil peripheral lymph node homing receptor

Jutila, MA; Kishimoto, T K; Butcher, EC

doi:10.1182/blood.v76.1.178.178

Cited by 53 publications

(14 citation statements)

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“…The activation of leukocytes by phorbol esters, chemoattractants, or various cytokines induces rapid (in minutes) endoproteolytic processing (shedding) of L-selectin from the cell surface [10][11][12]. We and others have shown that blocking L-selectin shedding dramatically reduces leukocyte rolling velocities and enhances leukocyte accumulation on endothelial ligands of L-selectin in vitro [13] and in vivo [14], which indicates that L-selectin shedding contributes in regulating L-selectin adhesion.…”

Section: Introductionmentioning

confidence: 82%

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Alexander

Kishimoto

Walcheck

2000

Journal of Leukocyte Biology

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The signaling factors that direct the rapid shedding of L-selectin from neutrophils upon chemoattractant stimulation are poorly understood. Protein kinase C (PKC) has been implicated, yet previous studies have relied on the use of phorbol esters and nonselective kinase inhibitors. We treated neutrophils with various selective kinase inhibitors to evaluate their effects on N-formylmethionyl-leucyl-phenylalanine (fMLP)-induced Lselectin shedding. We found that three selective inhibitors of PKC, structurally related to staurosporine, largely blocked both fMLP-and phorbol 12-myristate 13-acetate (PMA)-induced L-selectin shedding; however, these inhibitors did not affect fMLP-induced up-regulation of Mac-1 (CD11b/ CD18) expression, which has been shown not to involve PKC. Other selective serine, threonine, and tyrosine kinase inhibitors were found not to block fMLP-induced L-selectin shedding. These findings provide more definitive evidence for the role of PKC in chemoattractant-induced L-selectin proteolysis. It is interesting that certain highly selective PKC inhibitors, not structurally related to staurosporine, were found to directly induce Lselectin shedding from neutrophils. J. Leukoc. Biol. 67: 415-422; 2000.

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Section: Introductionmentioning

confidence: 82%

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Alexander

Kishimoto

Walcheck

2000

Journal of Leukocyte Biology

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“…Effects of cytokines and mitogens on endothelial cell ligands of leukocyte adhesion molecules have been studied in detail. IL1, TNF and LPS increase the expression of ICAM-1,ELAM-1 and VCAM-1 on human umbilical vein endothelial cells, and to promote the adherence of leukocytes to these activated endothelial cells [5].Therefore, it is interesting to find out that the same inducers also affect the homing receptor status of lymphocytes, peripheral blood leukocytes and bone marrow cells ( [16][17][18][31][32][33][34] and the present report). Thus, cytokines and mitogens can delicately control the extravasation of leukocytes at several steps.…”

Section: Molecular Form Of L-selectin On Cultured Cellsmentioning

confidence: 99%

Regulation of L‐selectin expression on cultured bone marrow leukocytes and their precursors

Salmi

Jalkanen

1992

Eur J Immunol

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L-selectin (LECAM-1, LAM-1, MEL-14 antigen, Dreg antigen) is one of the molecules controlling lymphocyte homing from the blood to peripheral lymph nodes and granulocyte adhesion to inflamed endothelium. In this work, regulation of L-selectin expression on mouse bone marrow cells was studied. L-selectin-negative cells were isolated by panning technique, cultured for 1-7 days with cytokines and mitogens, and L-selectin expression was analyzed by immunofluorescence staining. When cultured for 3 days with interleukin (IL) 1, IL 2, IL 5, IL 6, phytohemagglutinin, pokeweed mitogen or in the medium alone, 75%-85% of L-selectin-negative large cells (including granulocytes, macrophages/monocytes, blasts and their precursors) became L-selectin positive. In contrast, IL 3, IL 4, granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) prevented the induction of L-selectin in a time- and dose-dependent manner. GM-CSF was the most potent inhibitor and only 10%-15% of cells became L-selectin positive after 3 days of culture. Furthermore, L-selectin was down-regulated on cultured unselected bone marrow cells by IL 3, IL 4, GM-CSF and LPS stimulation. After culture, the relative molecular mass of L-selectin was 100 kDa, similar to the size of the granulocyte form of this antigen. Cultured cells adhered to high endothelial venules (HEV) only 10%-32% as effectively as freshly isolated bone marrow cells despite high levels of L-selectin expression. The phenotypic analysis and the HEV binding data indicate that after culturing L-selectin was almost exclusively expressed on bone marrow leukocytes of myeloid series, and on these cells it was not functional in mediating peripheral lymph node HEV binding. Overall, these results show that the expression of L-selectin can be modulated by regulating the maturation and differentiation of the cells in vitro. This supports the idea that different cytokines and mitogens may also be important in controlling migrational status of leukocytes in vivo.

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“…the cell upon activation with PMA or physiological activating factors, such as chemoattractants [6,27,28,39, 401.…”

Section: Characterization Of Bovine Leukocyte Lecam-1mentioning

confidence: 99%

Characterization of the bovine peripheral lymph node homing receptor: a lectin cell adhesion molecule (LECAM)

et al. 1992

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The phenomenon of tissue-specific homing of lymphocyte populations has been most clearly shown in larger domestic animals, such as the sheep and cow, yet the molecular interactions which control these processes in these animals have not been defined. Here we tested the cross-reactivity of four anti-human peripheral lymph node homing receptor (LECAM-1) (also known as LAM-1, LEC-CAM-1, Leu-8, TQ-1, or human equivalent of gp90 MEL-14) antibodies on bovine lymphocytes. These antibodies stained all bovine neutrophils and monocytes, and variable numbers of peripheral blood lymphocytes, as determined by flow cytometry. In young calves (less than 1 month old) virtually all circulating lymphocytes expressed LECAM-1, whereas the percentage of positive lymphocytes in older animals (greater than 1 year) varied from 17%-67%. Bovine LECAM-1 was rapidly lost from the cell surface of PMA-activated and chymotrypsin-treated cells. Anti-LECAM-1 monoclonal antibody blocked greater than 80% of bovine lymphocyte binding to peripheral lymph node high endothelial venules (HEV). Since the lectin domain of LECAM-1 is thought to mediate lymphocyte-HEV adhesion, we sought to establish further the similarity of the bovine, mouse, and human molecules by comparing nucleotide sequences in this region of the molecule. The polymerase chain reaction (PCR) was used to specifically clone the bovine lectin domain from single-strand cDNA. Subsequent sequencing showed an identity of greater than 80% at the nucleotide level with the human and mouse molecules. The predicted amino acid sequences were also highly conserved. Though striking similarities were seen between the bovine, mouse and human molecule, indicating evolutionary conservation of this family of proteins, notable differences were detected. The nucleotide sequence of the bovine lectin domain predicts one additional N-linked glycosylation site compared to mouse and human. Preliminary analysis suggested a more tissue-restricted expression of LECAM-1 in the compared to the human and mouse, which correlates with a better separation of lymphocyte homing phenotypes seen in these larger animals. Virtually all peripheral lymph node lymphocytes in 6-month-old calves expressed LECAM-1, whereas, ileal Peyer's patch lymphocytes were predominantly negative. Finally, by testing anti-human LECAM-1 antibodies in a different species we have established the co-expression of antigenic epitopes on leucocyte LECAM-1 and a molecule(s) expressed by endothelial cells.

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Regulation and lectin activity of the human neutrophil peripheral lymph node homing receptor

Cited by 53 publications

References 0 publications

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Regulation of L‐selectin expression on cultured bone marrow leukocytes and their precursors

Characterization of the bovine peripheral lymph node homing receptor: a lectin cell adhesion molecule (LECAM)

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