Mitochondrial reactive oxygen species regulate spatial profile of proinflammatory responses in lung venular capillaries

Kaushik Parthasarathi, Hideo Ichimura, Sadiqa Quadri, Andrew Issekutz, Jahar Bhattacharya

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Cytokine-induced lung expression of the endothelial cell (EC) leukocyte receptor P-selectin initiates leukocyte rolling. To understand the early EC signaling that induces the expression, we conducted real-time digital imaging studies in lung venular capillaries. To compare receptor- vs nonreceptor-mediated effects, we infused capillaries with respectively, TNF-α and arachidonate. At concentrations adjusted to give equipotent increases in the cytosolic Ca2+, both agents increased reactive oxygen species (ROS) production and EC P-selectin expression. Blocking the cytosolic Ca2+ increases abolished ROS production; blocking ROS production abrogated P-selectin expression. TNF-α, but not arachidonate, released Ca2+ from endoplasmic stores and increased mitochondrial Ca2+. Furthermore, Ca2+ depletion abrogated TNF-α responses partially, but arachidonate responses completely. These differences in Ca2+ mobilization by TNF-α and arachidonate were reflected in spatial patterning in the capillary in that the TNF-α effects were localized at branch points, while the arachidonate effects were nonlocalized and extensive. Furthermore, mitochondrial blockers inhibited the TNF-α- but not the arachidonate-induced responses. These findings indicate that the different modes of Ca2+ mobilization determined the spatial patterning of the proinflammatory response in lung capillaries. Responses to TNF-α revealed that EC mitochondria regulate the proinflammatory process by generating ROS that activate P-selectin expression.

Original languageEnglish (US)
Pages (from-to)7078-7086
Number of pages9
JournalJournal of Immunology
Volume169
Issue number12
DOIs
StatePublished - Dec 15 2002

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P-Selectin
Reactive Oxygen Species
Endothelial Cells
Lung
Leukocyte Rolling
Mitochondria
Leukocytes
Cytokines

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Mitochondrial reactive oxygen species regulate spatial profile of proinflammatory responses in lung venular capillaries. / Parthasarathi, Kaushik; Ichimura, Hideo; Quadri, Sadiqa; Issekutz, Andrew; Bhattacharya, Jahar.

In: Journal of Immunology, Vol. 169, No. 12, 15.12.2002, p. 7078-7086.

Research output: Contribution to journalArticle

Parthasarathi, Kaushik ; Ichimura, Hideo ; Quadri, Sadiqa ; Issekutz, Andrew ; Bhattacharya, Jahar. / Mitochondrial reactive oxygen species regulate spatial profile of proinflammatory responses in lung venular capillaries. In: Journal of Immunology. 2002 ; Vol. 169, No. 12. pp. 7078-7086.
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