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Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells.

Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells. Research Abstract Details 

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  • Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells. Abstract Text:

    Membrane-associated intercellular adhesion molecule-1 (mICAM-1; CD54) is constitutively expressed on the surface of type I alveolar epithelial cells (AEC). Soluble ICAM-1 (sICAM-1) may be produced by proteolytic cleavage of mICAM-1 or by alternative splicing of ICAM-1 mRNA. In contrast to inducible expression seen in most cell types, sICAM-1 is constitutively released by type I AEC and is present in normal alveolar lining fluid. Therefore, we compared the mechanism of sICAM-1 production in primary cultures of two closely juxtaposed cells in the alveolar wall, AEC and pulmonary microvascular endothelial cells (PVEC). AEC, but not PVEC, demonstrated high-level baseline expression of sICAM-1. Stimulation of AEC with TNFalpha or LPS resulted in minimal increase in AEC sICAM-1, whereas PVEC sICAM-1 was briskly induced in response to these signals. AEC sICAM-1 shedding was significantly reduced by treatment with a serine protease inhibitor, but not by cysteine, metalloprotease, or aspartic protease inhibitors. In contrast, none of these inhibitors effected sICAM-1 expression in PVEC. RT-PCR, followed by gel analysis of total RNA, suggests that alternatively spliced fragments are present in both cell types. However, a 16-mer oligopeptide corresponding to the juxtamembrane region of mICAM-1 completely abrogated sICAM-1 shedding in AEC but reduced stimulated PVEC sICAM-1 release by only 20%. Based on these data, we conclude that the predominant mechanism of sICAM-1 production likely differs in the two cell types from opposite sides of the alveolar wall.

    Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells. Publishing Authors By Initials

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    Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: American journal of physiology. Lung cellular and

    VOLUME: 294

    Page Numbers: L807-14

    Journal Abbreviation: Am. J. Physiol. Lung Cell Mol.

    ISSN: 1040-0605

    DAY: 15

    MONTH: 02

    YEAR: 2008

    Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells. Information

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    LANGUAGE: eng

    NlmUniqueID: 100901229

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    Grant and Affiliation Information for Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells.

    AFFILIATION: Pulmonary Section (111G Veterans Affairs Medical Center, 2215 Fuller Road, Ann Arbor, MI 48105. mpmendez@umich.edu).

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Am J Physiol Lung Cell Mol Phy

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