Ectodomain shedding

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Ectodomain shedding is a proteolytic process occurring at the surface of cells that regulates the density of cell surface receptors and the release of soluble proinflammatory factors.

The a disintegrin and metalloproteinase-17 (ADAM17), originally referred to as TNFalpha converting enzyme (TACE), is a key protease that mediates ectodomain shedding.  ADAM17 is constitutively expressed by leukocytes and its enzymatic activity is very rapidly induced upon their activation by various stimuli.

Natural killer cells

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Ectodomain shedding is a proteolytic process occurring at the surface of cells that regulates the density of cell surface receptors and the release of soluble proinflammatory factors.

The a disintegrin and metalloproteinase-17 (ADAM17), originally referred to as TNFalpha converting enzyme (TACE), is a key protease that mediates ectodomain shedding.  ADAM17 is constitutively expressed by leukocytes and its enzymatic activity is very rapidly induced upon their activation by various stimuli.

Neutrophil recruitment

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Neutrophils (polymorphonuclear cells or granulocytes) are terminally differentiated upon entering the blood from the bone marrow and are the most abundant type of immune cell in the circulation of humans and in the tissue during acute inflammation. Neutrophil recruitment from the blood into the underlying affected tissue is orchestrated, in part, by various families of adhesion molecules, chemokines, cytokines, and products of invading microorganisms. Neutrophils are a key source of local and systemic pro-inflammatory cytokines during acute inflammation. Neutrophils also generate chemotactic signals that attract monocytes and dendritic cells and influence their differentiation, and they secrete factors that drive T and B cell proliferation and differentiation. Neutrophils initiate the resolution of inflammation and play an important role in wound healing by instigating their own death (apoptosis) following pathogen engulfment (phagocytosisand by promoting macrophage accumulation. These macrophage then dispose of the apoptotic neutrophils by phagocytosis.

T CELL AND CANCER CELL MARKER: CHO-131

The monoclonal antibody CHO-131 (mouse IgM) recognizes a specific carbohydrate structure (core-2 O-glycan containing sLeX).  This carbohydrate is a high affinity ligand for the Selectin adhesion molecules (1).  CHO-131 reactivity provides a phenotypic marker for cells that bind to the Selectins (2, 3), which includes human neutrophils and a subset of T cells that migrate to sites of chronic inflammation in the skin, including psoriasis (4).  CHO-131 also detects certain carcinomas and its reactivity correlates with malignant progression and metastasis (5, 6).

REFERENCES:

  1. The monoclonal antibody CHO-131 binds to a core 2 O-glycan terminated with sialyl-Lewis x, which is a functional glycan ligand for P-selectinWalcheck, B., A. Leppanen, R. D. Cummings, R. N. Knibbs, L. M. Stoolman, S. R. Alexander, P. E. Mattila, and R. P. McEver. 2002. Blood 99: 4063–9.
  2. Structurally distinct requirements for binding of P-selectin glycoprotein ligand-1 and sialyl Lewis x to Anaplasma phagocytophilum and P-selectin. Yago, T., A. Leppanen, J. A. Carlyon, M. Akkoyunlu, S. Karmakar, E. Fikrig, R. D. Cummings, and R. P. McEver. 2003. J Biol Chem 278: 37987–37997.
  3. Functional analysis of the combined role of the O-linked branching enzyme core 2 beta1-6-N-glucosaminyltransferase and dimerization of P-selectin glycoprotein ligand-1 in rolling on P-selectin. Smith, M. J., B. R. Smith, M. B. Lawrence, and K. R. Snapp. 2004. J Biol Chem 279: 21984–21991.
  4. The monoclonal antibody CHO-131 identifies a subset of cutaneous lymphocyte-associated antigen T cells enriched in P-selectin-binding cells. Ni, Z., J. J. Campbell, G. Niehans, and B. Walcheck. 2006.  J Immunol 177: 4742–4748.
  5. Expression of the high-affinity selectin glycan ligand C2-O-sLeX by colon carcinoma cells. St Hill, C. A., K. M. Bullard, and B. Walcheck. 2005.  Cancer Lett. 217: 105–113.
  6. The high-affinity selectin glycan ligand C2-O-sLex and mRNA transcripts of the core 2 beta-1,6-N-acetylglusaminyltransferase (C2GnT1) gene are highly expressed in human colorectal adenocarcinomas. St Hill, C. A., M. Farooqui, G. Mitcheltree, H. E. Gulbahce, J. Jessurun, Q. Cao, and B. Walcheck. 2009.  BMC Cancer 9: 79.
  7. Increased expression of GCNT1 is associated with altered O-glycosylation of PSA, PAP, and MUC1 in human prostate cancers. Chen Z, Gulzar ZG, St. Hill C, Walcheck B, Brooks JD. 2014.  Prostrate. 74:1059