Polymorphonuclear leukocytes induce PDGF release from IL-1beta-treated endothelial cells: role of adhesion molecules and serine proteases
Research article published in Arteriosclerosis, thrombosis, and vascular biology (1998)
Abstract
Polymorphonuclear leukocytes (PMNs) and endothelial cells interact at sites of vascular injury during inflammatory response and during the development of atherosclerotic lesions. Such close proximity leads to the modulation of several of the biological functions of the 2 cell types. Because we have shown previously that PMNs enhance release of growth factors from resting endothelial cells, we decided to evaluate whether coincubation of PMNs with interleukin-1beta (IL-1beta)-stimulated human umbilical vein endothelial cells (HUVEC) could further modulate mitogen release from HUVEC. We found that PMN-HUVEC coincubation resulted in a 10-fold increase in mitogen release, compared with HUVEC alone (14+/-6 versus 1.3+/-0.1). When PMNs were incubated with IL-1beta-treated HUVEC, a further increase in mitogen release (up to 35-fold) was observed. The mitogenic activity was immunologically related to platelet-derived growth factor (PDGF) because the activity was abolished by an anti-PDGF antibody. PDGF-AB antigen, detected in low concentrations in conditioned medium from HUVEC alone, was increased 4-fold when IL-1beta or PMNs were incubated with HUVEC and dramatically upregulated (up to 40-fold) when PMNs were cocultured with IL-1beta-treated HUVEC. The presence of the protease inhibitor eglin C abolished mitogenic activity generation, suggesting a role for PMN-derived elastase and cathepsin G. Indeed, purified elastase and cathepsin G mimicked PMN-induced mitogen release from HUVEC. Because PMNs firmly adhered to IL-1beta-treated HUVEC, we investigated the role of cell-cell adhesion in mitogen release. Adhesion and PDGF release were inhibited by approximately 60% in the presence of anti-CD11a/CD18 and anti-intercellular adhesion molecule-1 monoclonal antibodies. This study suggests a new role for PMNs and their interaction with endothelium in pathological conditions in which intimal hyperplasia is a common feature.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Research article relevant to leech therapy and its derived compounds.
Por qué esto importa para la hirudoterapia
This study examined how polymorphonuclear leukocytes (PMNs) interact with IL-1β-stimulated human umbilical vein endothelial cells (HUVEC) to induce the release of platelet-derived growth factor (PDGF), finding up to 35-fold increases in mitogenic activity during PMN-HUVEC coculture. The protease inhibitor eglin C abolished the generation of mitogenic activity, and purified elastase and cathepsin G mimicked this PMN-induced release, implicating these proteases in the process. Adhesion molecules CD11a/CD18 and ICAM-1 also contributed, as their blockade inhibited both adhesion and PDGF release by approximately 60%. The abstract refers to eglin C only as "the protease inhibitor eglin C" with no mention of leeches, leech origin, or hirudotherapy; the study is conducted entirely in cultured cells.
Citación
Polymorphonuclear leukocytes induce PDGF release from IL-1beta-treated endothelial cells: role of adhesion molecules and serine proteases
Totani L · Arteriosclerosis, thrombosis, and vascular biology, 1998
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026