Neutrophils produce biologically active macrophage inflammatory protein-3α (MIP-3α)/CCL20 and MIP-3β/CCL19

Patrizia Scapini, Carlo Laudanna, Cristina Pinardi, Paola Allavena, Alberto Mantovani, Silvano Sozzani, Marco Antonio Cassatella

Research output: Contribution to journalArticle

Abstract

Macrophage inflammatory protein-3α (MIP-3α)/CCL20 and MIP-3β/CCL19 are members of the CC chemokine subfamily which exert their effects through specific receptors, CCR6 and CCR7, respectively. Previously, we have reported that human neutrophils have the capacity to produce a number of chemokines, including IL-8/CXCL8, GROα/CXCL1, IP-10/CXCL10, and MIG/CXCL9. Herein, we show that neutrophils also have the ability to express and release MIP-3α/CCL20 and MIP-3β/CCL19 when cultured with either LPS or TNF-α. We also report that MIP-3α/CCL20 and MIP-3β/CCL19 production by LPS-stimulated neutrophils is negatively modulated by IL-10. Remarkably, we found that supernatants harvested from stimulated neutrophils not only induced chemotaxis of both immature and mature dendritic dritic cells (DC), but also triggered rapid integrin-dependent adhesion of CCR6- and CCR7-expressing lymphocytes to purified VCAM-1 and ICAM-1, respectively. Importantly, both chemotaxis and rapid integrin-dependent adhesion were dramatically suppressed by anti-MIP-3α/CCL20 and anti-MIP-3β//CCL19 neutralizing antibodies, indicating that MIP-3α/ CCL20 and MIP-3β/CCL19 present in the supernatants were both biologically active. As these chemokines are primarily chemotactic for DC and specific lymphocyte subsets, the ability of neutrophils to produce MIP-3α/CCL20 and MIP-3β/CCL19 might be significant in orchestrating the recruitment of these cell types to the inflamed sites and therefore in contributing to the regulation of the immune response.

Original languageEnglish
Pages (from-to)1981-1988
Number of pages8
JournalEuropean Journal of Immunology
Volume31
Issue number7
DOIs
Publication statusPublished - 2001

Fingerprint

Macrophage Inflammatory Proteins
Neutrophils
Aptitude
Chemotaxis
Chemokines
Integrins
CCR6 Receptors
CCR7 Receptors
Anti-Inflammatory Agents
CC Chemokines
Vascular Cell Adhesion Molecule-1
Lymphocyte Subsets
Intercellular Adhesion Molecule-1
Neutralizing Antibodies
Interleukin-8
Interleukin-10
Dendritic Cells

Keywords

  • Eosinophil
  • IL-10
  • LPS
  • TNF-α

ASJC Scopus subject areas

  • Immunology

Cite this

Neutrophils produce biologically active macrophage inflammatory protein-3α (MIP-3α)/CCL20 and MIP-3β/CCL19. / Scapini, Patrizia; Laudanna, Carlo; Pinardi, Cristina; Allavena, Paola; Mantovani, Alberto; Sozzani, Silvano; Cassatella, Marco Antonio.

In: European Journal of Immunology, Vol. 31, No. 7, 2001, p. 1981-1988.

Research output: Contribution to journalArticle

Scapini, Patrizia ; Laudanna, Carlo ; Pinardi, Cristina ; Allavena, Paola ; Mantovani, Alberto ; Sozzani, Silvano ; Cassatella, Marco Antonio. / Neutrophils produce biologically active macrophage inflammatory protein-3α (MIP-3α)/CCL20 and MIP-3β/CCL19. In: European Journal of Immunology. 2001 ; Vol. 31, No. 7. pp. 1981-1988.
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T1 - Neutrophils produce biologically active macrophage inflammatory protein-3α (MIP-3α)/CCL20 and MIP-3β/CCL19

AU - Scapini, Patrizia

AU - Laudanna, Carlo

AU - Pinardi, Cristina

AU - Allavena, Paola

AU - Mantovani, Alberto

AU - Sozzani, Silvano

AU - Cassatella, Marco Antonio

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AB - Macrophage inflammatory protein-3α (MIP-3α)/CCL20 and MIP-3β/CCL19 are members of the CC chemokine subfamily which exert their effects through specific receptors, CCR6 and CCR7, respectively. Previously, we have reported that human neutrophils have the capacity to produce a number of chemokines, including IL-8/CXCL8, GROα/CXCL1, IP-10/CXCL10, and MIG/CXCL9. Herein, we show that neutrophils also have the ability to express and release MIP-3α/CCL20 and MIP-3β/CCL19 when cultured with either LPS or TNF-α. We also report that MIP-3α/CCL20 and MIP-3β/CCL19 production by LPS-stimulated neutrophils is negatively modulated by IL-10. Remarkably, we found that supernatants harvested from stimulated neutrophils not only induced chemotaxis of both immature and mature dendritic dritic cells (DC), but also triggered rapid integrin-dependent adhesion of CCR6- and CCR7-expressing lymphocytes to purified VCAM-1 and ICAM-1, respectively. Importantly, both chemotaxis and rapid integrin-dependent adhesion were dramatically suppressed by anti-MIP-3α/CCL20 and anti-MIP-3β//CCL19 neutralizing antibodies, indicating that MIP-3α/ CCL20 and MIP-3β/CCL19 present in the supernatants were both biologically active. As these chemokines are primarily chemotactic for DC and specific lymphocyte subsets, the ability of neutrophils to produce MIP-3α/CCL20 and MIP-3β/CCL19 might be significant in orchestrating the recruitment of these cell types to the inflamed sites and therefore in contributing to the regulation of the immune response.

KW - Eosinophil

KW - IL-10

KW - LPS

KW - TNF-α

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