A novel signaling mechanism between gas and blood compartments of the lung

Wolfgang M. Kuebler, Kaushik Parthasarathi, Ping M. Wang, Jahar Bhattacharya

Research output: Contribution to journalArticle

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Abstract

Propagation of inflammatory signals from the airspace to the vascular space is pivotal in lung inflammation, but mechanisms of intercompartmental signaling are not understood. To define signaling mechanisms, we microinfused single alveoli of blood-perfused rat lung with TNF-α, and determined in situ cytosolic Ca2+ concentration ([Ca2+](i)) by the fura-2 ratio method, cytosolic phospholipase A2 (cPLA2) activation and P-selectin expression by indirect immunofluorescence. Alveolar TNF-α increased [Ca2+](i) and activated cPLA2 in alveolar epithelial cells, and increased both endothelial [Ca2+](i) and P-selectin expression in adjoining perialveolar capillaries. All responses were blocked by pretreating alveoli with a mAb against TNF receptor 1 (TNFR1). Crosslinking alveolar TNFR1 also increased endothelial [Ca2+](i). However, the endothelial responses to alveolar TNF-α were blocked by alveolar preinjection of the intracellular Ca2+ chelator BAPTA- AM, or the cPLA2 blockers AACOCF3 and MAFP. The gap-junction uncoupler heptanol had no effect. We conclude that TNF-α induces signaling between the alveolar and vascular compartments of the lung. The signaling is attributable to ligation of alveolar TNFR1 followed by receptor-mediated [Ca2+](i) increases and cPLA2 activation in alveolar epithelium. These novel mechanisms may be relevant in the alveolar recruitment of leukocytes.

Original languageEnglish (US)
Pages (from-to)905-913
Number of pages9
JournalJournal of Clinical Investigation
Volume105
Issue number7
DOIs
StatePublished - Jan 1 2000

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Cytosolic Phospholipases A2
Tumor Necrosis Factor Receptors
Gases
Lung
P-Selectin
Blood Vessels
Heptanol
Alveolar Epithelial Cells
Fura-2
Gap Junctions
Indirect Fluorescent Antibody Technique
Chelating Agents
Ligation
Pneumonia
Leukocytes
Epithelium

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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A novel signaling mechanism between gas and blood compartments of the lung. / Kuebler, Wolfgang M.; Parthasarathi, Kaushik; Wang, Ping M.; Bhattacharya, Jahar.

In: Journal of Clinical Investigation, Vol. 105, No. 7, 01.01.2000, p. 905-913.

Research output: Contribution to journalArticle

Kuebler, Wolfgang M. ; Parthasarathi, Kaushik ; Wang, Ping M. ; Bhattacharya, Jahar. / A novel signaling mechanism between gas and blood compartments of the lung. In: Journal of Clinical Investigation. 2000 ; Vol. 105, No. 7. pp. 905-913.
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