Regulation of macrophage phagocytosis of apoptotic neutrophils by adhesion to fibronectin

J C McCutcheon, S P Hart, M Canning, K Ross, M J Humphries, I Dransfield

Research output: Contribution to journalArticlepeer-review


The potential for leukocyte-mediated host tissue damage during resolution of inflammatory responses is influenced by the rate at which extravasated apoptotic leukocytes are cleared from inflammatory sites. Regulation of macrophage capacity for clearance of apoptotic granulocytes is likely to be an important factor determining whether inflammation ultimately resolves or progresses to a chronic state. In this study we have investigated the molecular basis for rapid augmentation of macrophage phagocytosis of apoptotic neutrophils, which was observed following macrophage adhesion to fibronectin. We used a combination of monoclonal antibodies, blocking peptides, and recombinant fibronectin fragments to investigate the role of beta1 integrins in mediating the fibronectin effects. Blockade of alpha5beta1 or alpha4beta1 alone did not attenuate fibronectin-augmentation of phagocytosis. In addition, adhesion of macrophages to recombinant fibronectins lacking alpha4beta1 recognition motifs failed to promote phagocytosis of apoptotic neutrophils. Our results would be consistent with a model in which multiple fibronectin receptors, including beta1 integrins, act co-operatively to augment macrophage phagocytic responses. Together, these data suggest that the extracellular matrix environment of macrophages may provide regulatory signals that act indirectly to rapidly alter the potential for removal of apoptotic cells and influence the process of resolution of inflammation.

Original languageEnglish
Pages (from-to)600-7
Number of pages8
JournalJournal of leukocyte biology
Issue number5
Publication statusPublished - Nov 1998


  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Apoptosis
  • Cell Adhesion
  • Extracellular Matrix
  • Fibronectins
  • Humans
  • Inflammation
  • Integrin alpha4beta1
  • Integrins
  • Macrophages
  • Models, Biological
  • Neutrophils
  • Peptide Fragments
  • Phagocytosis
  • Receptors, Fibronectin
  • Receptors, Lymphocyte Homing
  • Recombinant Proteins
  • Signal Transduction
  • Vitronectin


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