A Bone Marrow Myeloid Progenitor Cell Enhances Mouse Alveolar Type II Cell Growth In Vitro.

The heat shock response is a highly conserved stress response that can transiently inhibit non-heat shock protein gene expression. Although heat shock protects against acute lung injury, its effects on lung cell gene expression are not known. We studied the in vitro effects of heat shock on the expression of several genes important to alveolar type II cells. Prior induction of heat shock transiently inhibited cytokine-mediated inducible nitric oxide synthase gene expression and cytokine-mediated manganese-superoxide dismutase mRNA expression in murine lung epithelium. In contrast, heat shock had no effect on expression of surfactant protein (SP) A or B mRNA, or SP-B peptide synthesis. Cell survival studies indicated that the inhibitory effects were not secondary to cytotoxicity. Previous heat shock also modestly enhanced the ability of cells to withstand oxidant stress. We conclude that in vitro heat shock has selective and transient inhibitory effects on alveolar type II cell gene expression. Transient inhibition of cytokine-inducible genes, with concomitant conservation of genes required for normal respiratory function (SP) may explain, in part, the mechanism by which heat shock protects during acute lung injury.

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Degradation of surfactant lipids and surfactant protein A by alveolar macrophages in vitro

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1995.268.5.l772 ◽

1995 ◽

Vol 268 (5) ◽

pp. L772-L780 ◽

Cited By ~ 19

Author(s):

J. R. Wright ◽

D. C. Youmans

Keyword(s):

Protein A ◽

Surfactant Protein ◽

Surfactant Protein A ◽

Alveolar Type ◽

Dependent Manner ◽

Type Ii ◽

Alveolar Type Ii Cell ◽

Degradation Rates ◽

Type Ii Cell

Pulmonary surfactant is synthesized and secreted into the airspaces by the alveolar type II cell. After it is secreted, surfactant undergoes a series of poorly understood transformations resulting in formation of a surface tension-reducing surface at the air-liquid interface. The by-products of the surface film and/or other products of surfactant metabolism are eventually cleared from the alveolar space. Both the alveolar type II cell and the macrophage are thought to be involved in surfactant clearance and have been shown to internalize surfactant lipid in vitro. The goal of the current investigation was to characterize further and to quantitate the role of the macrophage in surfactant clearance by investigating the uptake and metabolism of surfactant lipids and surfactant protein A (SP-A) by macrophages in vitro. SP-A enhanced the uptake of lipids by macrophages in a time-, temperature-, and concentration-dependent manner. In contrast, neither of the collagen-like proteins SP-D or C1q enhanced the uptake. Phosphatidylcholine was rapidly degraded by macrophages and the degradation occurred both in the presence and absence of SP-A. In addition, macrophages degrade SP-A by a process that is time- and temperature-dependent. These results and calculations of uptake and degradation rates suggest that macrophages may contribute significantly to the process of surfactant clearance.

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