Particulate matter induces cytokine expression in human bronchial epithelial cells.

The present study was designed to determine cytokines produced by primary human bronchial epithelial cells (HBECs) exposed to ambient air pollution particles (EHC-93). Cytokine messenger RNA (mRNA) was measured using a ribonuclease protection assay and cytokine protein production by enzyme-linked immunosorbent assay. Primary HBECs were freshly isolated from operated lung, cultured to confluence, and exposed to 10 to 500 microg/ml of a suspension of ambient particulate matter with a diameter of less than 10 microm (PM(10)) for 2, 8, and 24 h. The mRNA levels of leukemia inhibitory factor (LIF), granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1alpha, and IL-8 were increased after exposure to PM(10), and this increase was dose-dependent between 100 (P < 0.05) and 500 (P < 0.05) microg/ml of PM(10) exposure. The concentrations of LIF, GM-CSF, IL-1beta, and IL-8 protein measured in the supernatant collected at 24 h increased in a dose- dependent manner and were significantly higher than those in the control nonexposed cells. The soluble fraction of the PM(10) (100 microg/ml) did not increase these cytokine mRNA levels compared with control values and were significantly lower compared with HBECs exposed to 100 microg/ml of PM(10) (LIF, IL-8, and IL-1beta; P < 0.05), except for GM-CSF mRNA (P = not significant). We conclude that primary HBECs exposed to ambient PM(10) produce proinflammatory mediators that contribute to the local and systemic inflammatory response, and we speculate that these mediators may have a role in the pathogenesis of cardiopulmonary disease associated with particulate air pollution.

[1]  A. Smith,et al.  Leukemia inhibitory factor differentiation-inhibiting activity/human interleukin for DA cells augments proliferation of human hematopoietic stem cells. , 1990, Blood.

[2]  I. Kushner,et al.  Acute-phase proteins and other systemic responses to inflammation. , 1999, The New England journal of medicine.

[3]  E. Platzer Human hemopoietic growth factors , 1989, European journal of haematology.

[4]  J. Gamble,et al.  Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival. , 1986, The Journal of clinical investigation.

[5]  I. Adamson,et al.  Pulmonary toxicity of an atmospheric particulate sample is due to the soluble fraction. , 1999, Toxicology and applied pharmacology.

[6]  A. Mantovani,et al.  In vitro and in vivo activation of endothelial cells by colony-stimulating factors. , 1991, The Journal of clinical investigation.

[7]  L. V. Van Pelt,et al.  A single dose of granulocyte-macrophage colony-stimulating factor induces systemic interleukin-8 release and neutrophil activation in healthy volunteers. , 1996, Blood.

[8]  J. Hogg,et al.  The human bone marrow response to acute air pollution caused by forest fires. , 2000, American journal of respiratory and critical care medicine.

[9]  I. Adamson,et al.  Acute pulmonary toxicity of urban particulate matter and ozone. , 1997, The American journal of pathology.

[10]  J. Carter,et al.  Disruption of normal iron homeostasis after bronchial instillation of an iron-containing particle. , 1998, The American journal of physiology.

[11]  C. Pope,et al.  Acute effects of PM10 pollution on pulmonary function of smokers with mild to moderate chronic obstructive pulmonary disease. , 1993, The American review of respiratory disease.

[12]  D. Knight,et al.  Leukemia inhibitory factor (LIF) and LIF receptor in human lung. Distribution and regulation of LIF release. , 1999, American journal of respiratory cell and molecular biology.

[13]  D. Dockery,et al.  Particulate air pollution as a predictor of mortality in a prospective study of U.S. adults. , 1995, American journal of respiratory and critical care medicine.

[14]  J. Hogg,et al.  Polymorphonuclear Leukocytes Released from the Bone Marrow Preferentially Sequester in Lung Microvessels , 1997, Microcirculation.

[15]  T. Kishimoto,et al.  Gp130 and the interleukin-6 family of cytokines. , 1997, Annual review of immunology.

[16]  J. Hogg,et al.  Polymorphonuclear leukocyte (PMN) migration in streptococcal pneumonia: comparison of older PMN with those recently released from the marrow. , 1996, American journal of respiratory cell and molecular biology.

[17]  O. Houcine,et al.  Diesel exhaust particles are taken up by human airway epithelial cells in vitro and alter cytokine production. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[18]  J. Carter,et al.  Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent. , 1997, Toxicology and applied pharmacology.

[19]  J. Hogg,et al.  Phagocytosis of particulate air pollutants by human alveolar macrophages stimulates the bone marrow. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[20]  K. BéruBé,et al.  Bioreactivity of carbon black and diesel exhaust particles to primary Clara and type II epithelial cell cultures. , 1999, Occupational and environmental medicine.

[21]  D. Dockery,et al.  An association between air pollution and mortality in six U.S. cities. , 1993, The New England journal of medicine.

[22]  R. Davies,et al.  Airway epithelial cells, cytokines, and pollutants. , 1999, American journal of respiratory and critical care medicine.

[23]  J. Hogg,et al.  Polymorphonuclear leukocytes released from the bone marrow and acute lung injury. , 1999, Chest.

[24]  S. Tyagi Homocysteine redox receptor and regulation of extracellular matrix components in vascular cells. , 1998, American journal of physiology. Cell physiology.

[25]  J. Hogg,et al.  Cigarette smoking causes sequestration of polymorphonuclear leukocytes released from the bone marrow in lung microvessels. , 1999, American journal of respiratory cell and molecular biology.

[26]  P. Barnes,et al.  Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. , 1996, American journal of respiratory and critical care medicine.

[27]  H. Bayram,et al.  The effect of diesel exhaust particles on cell function and release of inflammatory mediators from human bronchial epithelial cells in vitro. , 1998, American journal of respiratory cell and molecular biology.

[28]  T. Horie,et al.  Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation. , 2000, American journal of respiratory and critical care medicine.

[29]  T. Casale,et al.  Interleukin-8 is a potent mediator of eosinophil chemotaxis through endothelium and epithelium. , 1995, The American journal of physiology.

[30]  R. Devlin,et al.  Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production. , 1996, Toxicology and applied pharmacology.

[31]  J. Hogg,et al.  Phagocytosis of small carbon particles (PM10) by alveolar macrophages stimulates the release of polymorphonuclear leukocytes from bone marrow. , 1997, American journal of respiratory and critical care medicine.

[32]  A. Imrich,et al.  Analysis of air pollution particulate-mediated oxidant stress in alveolar macrophages. , 1998, Journal of toxicology and environmental health. Part A.

[33]  S. Weiss Tissue destruction by neutrophils. , 1989, The New England journal of medicine.

[34]  J. Carter,et al.  Copper-dependent inflammation and nuclear factor-kappaB activation by particulate air pollution. , 1998, American journal of respiratory cell and molecular biology.