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May 1, 1994Biochemical JournalOpen Access

Immunocomplexes stimulate different signalling events to chemoattractants in the neutrophil and regulate L-selectin and beta 2-integrin expression differently.

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Authors

YMYair MoladTel Aviv UniversityKHKathleen HainesConnecticut Children's Medical CenterDAD. C. AndersonUniversity of Colorado Denver

Discussion

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Implication

Laboratory study demonstrates divergent regulation of L-selectin and CD11b/CD18 in neutrophils by immunocomplexes versus chemoattractants, indicating distinct downstream signalling mechanisms.

Key Points

  • To determine how chemoattractants, immunocomplexes, and transforming growth factor beta regulate the surface expression of L-selectin and CD11b/CD18 in neutrophils, along with their underlying signal-transduction pathways.
  • Treated isolated neutrophils with G-protein-coupled chemoattractants (C5a, IL-8, FMLP, substance P), BSA-anti-BSA immunocomplexes targeting Fc gamma receptors, or TGF-beta 1 across multiple concentrations (n=5).
  • Measured surface levels of L-selectin shedding and beta 2-integrin CD11b/CD18 expression via quantitative assays.
  • Assessed intracellular mechanisms by inhibiting actin microfilaments with cytochalasin B (5 µg/ml) and tyrosine kinases with tyrphostin-25 (25 µM), alongside measuring diacylglycerol synthesis and calcium flux.
  • Fc gamma receptor occupancy by immunocomplexes induced CD11b/CD18 upregulation at concentrations that did not alter L-selectin expression (EC50 9 µg/ml vs. 350 µg/ml, P < 0.00001, n=5).
  • Recombinant C5a, recombinant IL-8, and FMLP concurrently increased CD11b/CD18 expression (170–260% of basal, P < 0.001, n=5) and reduced L-selectin (56–75% reduction, P < 0.001, n=5) at similar potencies (EC50 of 2, 5, and 3 nM, respectively).
  • Cytochalasin B amplified diacylglycerol generation in response to FMLP but not immunocomplexes, while substance P and TGF-beta 1 showed no regulatory effect on either adhesion molecule.

Cite This Study

Molad et al. (1994) studied this question.

synapsesocial.com/papers/6a7055e9febe604dd70920b5https://doi.org/10.1042/bj2990881
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Also Consider

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  1. 1Tyrosine-specific protein phosphorylation during activation of human neutrophils1990 · 90 citations
  2. 2Neuropeptides and inflammation. A somatostatin analog as a selective antagonist of neutrophil activation by substance P1992 · 69 citations
  3. 3Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule.1990 · 432 citations
  4. 4Human neutrophils increase expression of C3bi as well as C3b receptors upon activation.1984 · 385 citations