Smoke extract stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activities

Accumulation of monocytes and neutrophils and fibrous distortion of the airway are characteristics of airway disease secondary to smoking. The presence of inflammatory cells and fibrosis correlate, and, therefore, we postulated that lung fibroblasts might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, human fetal lung (HFL1) fibroblasts were cultured, and the supernatant fluid was evaluated for neutrophil (NCA) and monocyte (MCA) chemotactic activities with a blind well chamber technique. HFL1 fibroblasts released chemotactic activity in response to smoke extract in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis showed that the activity was predominantly chemotactic. Partial characterization of the released chemotactic activity revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of both NCA and MCA. Molecular-sieve chromatography revealed that NCA and MCA were heterogeneous. NCA was inhibited by anti-human interleukin (IL)-8 and anti-granulocyte colony-stimulating factor antibodies and a leukotriene (LT) B(4)-receptor antagonist. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) and anti-monocyte chemoattractant protein (MCP)-1 antibodies and an LTB(4)-receptor antagonist inhibited MCA. Immunoreactive IL-8, granulocyte colony-stimulating factor, GM-CSF, and MCP-1 significantly increased in culture supernatant fluid in response to smoke extract. Finally, smoke extract augmented the expression of mRNAs of IL-8, GM-CSF, and MCP-1. These data demonstrate that lung fibroblasts release NCA and MCA in response to smoke extract and suggest that lung fibroblasts may modulate the inflammatory cell recruitment into the lung.

Medienart:

E-Artikel

Erscheinungsjahr:

1999

Erschienen:

1999

Enthalten in:

Zur Gesamtaufnahme - volume:277

Enthalten in:

The American journal of physiology - 277(1999), 6 vom: 20. Dez., Seite L1149-57

Sprache:

Englisch

Beteiligte Personen:

Sato, E [VerfasserIn]
Koyama, S [VerfasserIn]
Takamizawa, A [VerfasserIn]
Masubuchi, T [VerfasserIn]
Kubo, K [VerfasserIn]
Robbins, R A [VerfasserIn]
Nagai, S [VerfasserIn]
Izumi, T [VerfasserIn]

Links:

Volltext

Themen:

134578-96-4
143011-72-7
1HGW4DR56D
83869-56-1
98600C0908
Chemokine CCL2
Chemokine CCL5
Cycloheximide
Granulocyte Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Immunosuppressive Agents
Interleukin-8
Isoquinolines
Journal Article
Leukotriene B4
ONO-LB 457
Phenylpropionates
Platelet Aggregation Inhibitors
Platelet Membrane Glycoproteins
Platelet activating factor receptor
Protein Synthesis Inhibitors
Pyridinium Compounds
Receptors, Cell Surface
Receptors, G-Protein-Coupled
SMQ997EQ85
TCV 309
Tetrahydroisoquinolines
Transforming Growth Factor beta

Anmerkungen:

Date Completed 20.01.2000

Date Revised 13.12.2023

published: Print

Citation Status MEDLINE

doi:

10.1152/ajplung.1999.277.6.L1149

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM105306738