Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Smoke extract stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activities. 1060 Aug 85

Activation of the kallikrein-kinin system in lung injury has long been recognized. However, the effects of bradykinin (BK) on human lung fibroblasts (HLF) remain to be elucidated. We determined whether BK stimulates HLF to release chemotactic activity for neutrophils and monocytes (NCA and MCA, respectively). We evaluated HLF supernatant fluids for chemotactic activity through a blind-well chamber technique. HLF released NCA and MCA in a dose- and time-dependent manner in response to BK. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular sieve column chromatography revealed that both NCA and MCA had multiple chemotactic peaks. NCA was inhibited by a leukotriene (LT) B(4) receptor antagonist and by antibodies to interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF). MCA was attenuated by the LTB(4) receptor antagonist and by antibodies to monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and transforming growth factor (TGF)-beta. Both the LTB(4) receptor antagonist and these antibodies inhibited chemotactic activity of the molecular weights corresponding to MCP-1, GM-CSF, and TGF-beta, separated by column chromatography. The concentrations of IL-8, G-CSF, MCP-1, GM-CSF, and TGF-beta in supernatant fluids increased significantly in a time-dependent manner in response to BK. The receptors responsible for the release of NCA, MCA, and individual chemokines included both BKB(1) and BKB(2) receptors. These data suggest that BK may stimulate lung fibroblasts to release inflammatory cytokines, which may modulate lung inflammation.
 ...
PMID:Bradykinin stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activity. 1061 68

Cyclophosphamide is an alkylating antineoplastic agent used in several conditions. However, little is known about the mechanism of its pulmonary toxicity. In the present study, we determined that human lung fibroblasts release activity for neutrophils and monocytes in response to cyclophosphamide in a dose- and time-dependent manner. Checkerboard analysis revealed that both neutrophil and monocyte activities were chemotactic. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular-sieve column chromatography revealed that both neutrophil (NCA) and monocyte (MCA) chemotactic activities had multiple peaks. NCA was inhibited by a leukotriene B(4) receptor antagonist and anti-interleukin-8 and anti-granulocyte colony-stimulating factor antibodies. MCA was attenuated by a leukotriene B(4) receptor antagonist and anti-monocyte chemoattractant protein-1 and anti-granulocyte-macrophage colony-stimulating factor antibodies. The concentrations of interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor significantly increased in response to cyclophosphamide. These data suggest that lung fibroblasts may modulate inflammatory cell recruitment into the lung by releasing NCA and MCA in response to cyclophosphamide.
 ...
PMID:Cyclophosphamide stimulates lung fibroblasts to release neutrophil and monocyte chemoattractants. 1135 Jul 99