Surfactant protein-A receptor-mediated inhibition of calcium signaling in alveolar type II cells.

D. S. Strayer, L. Korutla, A. P. Thomas

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Receptor-mediated inhibition of cellular activating signals is not well understood. Type II alveolar cells secrete surfactant in response to such secretagogs as terbutaline, calcium (Ca) ionophores (e.g., ionomycin [Io]), and adenosine triphosphate (ATP). A cell membrane receptor for SP-A, one of the surfactant proteins, regulates secretion by negative feedback. We used quantitative fluorescence microscopy to study the effects of SP-A on alterations in cytosolic Ca2+ ([Ca2+]i) elicited by surfactant secretagogs. Freshly isolated type II cells were loaded with Fura-2, then treated with secretagog, in the presence or absence of SP-A. Io and ATP produced biphasic increases in cytosol [Ca2+]i, reflecting first Ca2+ release from intracellular stores, and then influx through the cell membrane. Thapsigargin (TG) and Io directly initiate Ca2+ release; ATP elicits Ca2+ release via receptor-mediated mechanisms. Ca2+ release causes cell membrane Ca channels to open by as yet poorly understood mechanisms. Io itself acts as an additional Ca2+ channel. SP-A blocks much of the Ca2+ release and some of the Ca2+ influx elicited by these secretagogs. Antibody against SP-A receptor restores secretagog-induced Ca2+ fluxes from inhibition by SP-A, confirming that the inhibitory activity of SP-A is mediated through its receptor. Type II cells incubated in Ca2+-free medium plus SP-A show diminished Ca2+ release responses to TG or ATP, suggesting that the action of SP-A to prevent secretagog initiated increases in [Ca2+]i may reflect its ability to block Ca2+ release from cytoplasmic Ca stores. The feedback inhibition of surfactant secretion by SP-A may, correspondingly, be a manifestation of this effect. Because recent work suggests that TGF-beta also inhibits Ca2+ fluxes, SP-A and TGF-beta could be representative of a group of physiologic regulators that act by modulating intracellular Ca signaling.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalReceptors & signal transduction
Issue number2
StatePublished - 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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