Functional and genomic changes induced by alveolar transmigration in human neutrophils

Christopher D. Coldren, Jerry A. Nick, Katie R. Poch, Malcolm D. Woolum, Brian W. Fouty, James M. O'Brien, Michael P. Gruber, Martin R. Zamora, Daiva Svetkauskaite, Don A. Richter, Qianbin He, Sung Park Jong, Katherine H. Overdier, Edward Abraham, Mark W. Geraci

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Although the accumulation of neutrophils in the lungs and airways is common to many inflammatory lung diseases, including acute lung injury, the alterations that neutrophils undergo as they leave the peripheral circulation and migrate into the lungs have not been well characterized. Human volunteers were exposed to endotoxin by bronchoscopic instillation. The resulting air space neutrophil accumulation and peripheral blood neutrophils were isolated 16 h later, compared with circulating neutrophils isolated before or after to the pulmonary endotoxin exposure, and compared with circulating neutrophils exposed to endotoxin in vitro. Microarray analysis was performed on air space, circulatory, and in vitro endotoxin-stimulated neutrophils. Functional analysis included the determination of neutrophil apoptosis, chemotaxis, release of cytokines and growth factors, and superoxide anion release. Dramatic gene expression differences were apparent between air space and circulating neutrophils: ∼15% of expressed genes have altered expression levels, including broad increases in inflammatory- and chemotaxis-related genes, as well as antiapoptotic and IKK-activating pathways. Functional analysis of air space compared with circulating neutrophils showed increased superoxide release, diminished apoptosis, decreased IL-8-induced chemotaxis, and a pattern of IL-8, macrophage inflammatory protein-1β, monocyte chemoattractant protein-1, and tumor necrosis factor-α release different from either unstimulated or LPS-stimulated circulating neutrophils. Many of these changes are not elicited by in vitro treatment with endotoxin. Limited differences were detected between circulating neutrophils isolated before and 16 h after pulmonary endotoxin instillation. These results suggest that neutrophils sequestered in the lung become fundamentally different from those resident in the circulation, and this difference is distinct from in vitro activation with endotoxin.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number6
DOIs
StatePublished - Dec 2006
Externally publishedYes

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Neutrophils
Endotoxins
Chemotaxis
Lung
Air
Interleukin-8
Superoxides
Apoptosis
Macrophage Inflammatory Proteins
Acute Lung Injury
Chemokine CCL2
Microarray Analysis
Lung Diseases
Genes
Volunteers
Intercellular Signaling Peptides and Proteins
Tumor Necrosis Factor-alpha
Cytokines
Gene Expression
In Vitro Techniques

Keywords

  • Acute lung injury
  • Acute respiratory distress syndrome
  • Inflammation
  • Sepsis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Functional and genomic changes induced by alveolar transmigration in human neutrophils. / Coldren, Christopher D.; Nick, Jerry A.; Poch, Katie R.; Woolum, Malcolm D.; Fouty, Brian W.; O'Brien, James M.; Gruber, Michael P.; Zamora, Martin R.; Svetkauskaite, Daiva; Richter, Don A.; He, Qianbin; Jong, Sung Park; Overdier, Katherine H.; Abraham, Edward; Geraci, Mark W.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 291, No. 6, 12.2006.

Research output: Contribution to journalArticle

Coldren, CD, Nick, JA, Poch, KR, Woolum, MD, Fouty, BW, O'Brien, JM, Gruber, MP, Zamora, MR, Svetkauskaite, D, Richter, DA, He, Q, Jong, SP, Overdier, KH, Abraham, E & Geraci, MW 2006, 'Functional and genomic changes induced by alveolar transmigration in human neutrophils', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 291, no. 6. https://doi.org/10.1152/ajplung.00097.2006
Coldren, Christopher D. ; Nick, Jerry A. ; Poch, Katie R. ; Woolum, Malcolm D. ; Fouty, Brian W. ; O'Brien, James M. ; Gruber, Michael P. ; Zamora, Martin R. ; Svetkauskaite, Daiva ; Richter, Don A. ; He, Qianbin ; Jong, Sung Park ; Overdier, Katherine H. ; Abraham, Edward ; Geraci, Mark W. / Functional and genomic changes induced by alveolar transmigration in human neutrophils. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2006 ; Vol. 291, No. 6.
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AB - Although the accumulation of neutrophils in the lungs and airways is common to many inflammatory lung diseases, including acute lung injury, the alterations that neutrophils undergo as they leave the peripheral circulation and migrate into the lungs have not been well characterized. Human volunteers were exposed to endotoxin by bronchoscopic instillation. The resulting air space neutrophil accumulation and peripheral blood neutrophils were isolated 16 h later, compared with circulating neutrophils isolated before or after to the pulmonary endotoxin exposure, and compared with circulating neutrophils exposed to endotoxin in vitro. Microarray analysis was performed on air space, circulatory, and in vitro endotoxin-stimulated neutrophils. Functional analysis included the determination of neutrophil apoptosis, chemotaxis, release of cytokines and growth factors, and superoxide anion release. Dramatic gene expression differences were apparent between air space and circulating neutrophils: ∼15% of expressed genes have altered expression levels, including broad increases in inflammatory- and chemotaxis-related genes, as well as antiapoptotic and IKK-activating pathways. Functional analysis of air space compared with circulating neutrophils showed increased superoxide release, diminished apoptosis, decreased IL-8-induced chemotaxis, and a pattern of IL-8, macrophage inflammatory protein-1β, monocyte chemoattractant protein-1, and tumor necrosis factor-α release different from either unstimulated or LPS-stimulated circulating neutrophils. Many of these changes are not elicited by in vitro treatment with endotoxin. Limited differences were detected between circulating neutrophils isolated before and 16 h after pulmonary endotoxin instillation. These results suggest that neutrophils sequestered in the lung become fundamentally different from those resident in the circulation, and this difference is distinct from in vitro activation with endotoxin.

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