Phosphatidylinositol 3-kinase mediates chemoattractant-stimulated, CD11b/CD18-dependent cell-cell adhesion of human neutrophils: Evidence for an ERK-independent pathway

Constance Capodici, Simon Hanft, Marianne Feoktistov, Michael H. Pillinger

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

We examined the role of phosphatidylinositol 3-kinase (PI 3-K) in FMLP- stimulated cell-cell adhesion of human neutrophils. The specific PI 3-K inhibitors wortmannin and LY294002 inhibited neutrophil homotypic aggregation stimulated by chemoattractants such as FMLP (50% inhibitory concentration (IC50) ≃ 11 nM and 13 μM, respectively) but not PMA. Wortmannin also inhibited FMLP-stimulated adhesion of neutrophils to human endothelial cell monolayers, suggesting a common signaling pathway for homotypic and heterotypic adhesion. Neither CD11b/CD18 expression nor expression of an activation-specific epitope of CD11b/CD18 was affected by wortmannin in FMLP- stimulated cells. Moreover, wortmannin also inhibited the aggregation of egranulate neutrophil cytoplasts that lack the capacity for CD11b/CD18 up- regulation. Although wortmannin inhibited neutrophil lysosomal enzyme release, it had no effect on FMLP-stimulated up-regulation of CD35 in intact neutrophils, suggesting discrepant signaling pathways for specific granule degranulation and secretory vesicle release. Aggregation of human neutrophils is associated with activation of the mitogen-activated protein kinases Erk1 and -2, and Erk is activated in response to PI 3-K in some cell types. However, wortmannin inhibited FMLP stimulation of neutrophil Erk only at concentrations (IC50 ≤ 1 μM) inconsistent with an effect on PI 3-K. Our data indicate that PI 3-K mediates neutrophil adhesion by a mechanism independent of CD11b/CD18 up-regulation, suggesting that PI 3-K acts either parallel to, or downstream of, Erk.

Original languageEnglish (US)
Pages (from-to)1901-1909
Number of pages9
JournalJournal of Immunology
Volume160
Issue number4
StatePublished - Feb 15 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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