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Eicosanoid modulation of stress fibers in cultured bovine aortic endothelial cells

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Abstract

Leukotrienes (LT) B4, LTD4, and thromboxanes (TX) are cytotoxic, and increase microvascular permeability. Because endothelial stress fibers are theorized to be part of the cytoskeletal mechanism by which microvessels maintain their barrier function, the effect of these eicosanoids on stress fibers in bovine aortic endothelial cells was tested. LTB4, LTD4, and TXB2 each decreased stress fiber numbers by 93%, 62%, and 66%, respectively, when compared to controls (P < 0.01). In contrast, endothelial cells treated with prostacyclin (PGI2) at 10−7 M, produced a significant increase (P >0.01) in stress fiber numbers, 211% to that of controls. Azaprostanoic acid (13-APA) and FPL55712, receptor antagonists to TX and slowreacting substance of anaphylaxis (SRS) receptors, respectively, the cyclooxygenase inhibitor ibuprofen, and the TX synthase inhibitors imidazole and ketoconazole were used to test for possible endothelial cell receptor mediation and de novo prostanoid synthesis associated with inflammatory eicosanoid-induced disassembly of stress fibers. Each pharmacologic agent inhibited the LTD4- and TXB2-induced decreases in stress fibers; LTB4-stimulated stress fiber decreases were inhibited only by pretreatment with TX synthase blockers. These data suggest that increased permeability associated with inflammatory eicosanoid metabolites may have as a common target stress fiber disassembly, and the mechanism may be receptor-mediated. That cyclooxygenase and TX synthase blockers inhibited the eicosanoid action suggests that endogenous TX synthesis may be a step in the mechanism. PGI2 enhancement of the microvascular barrier may be related to the effect of PGI2 on promoting stress fiber assembly. In summary, endothelial cell synthesized autocoids derived from arachidonic acid may help to regulate microvascular permeability by way of their action on stress fiber assembly/dissassembly, and unbalanced prostanoid secretion by way of LT stimulation may result in a loss of the microvascular barrier and increased permeability.

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Authors and Affiliations

  1. Biological Science Center, 2 Cummington Street, 02215, Boston, Massachusetts

    Seth L. Welles & David Shepro

  2. Department of Surgery, Boston University, 2 Cummington Street, 02215, Boston, Massachusetts

    David Shepro

  3. Department of Surgery, Harvard Medical School, 02115, Boston, Massachusetts

    Herbert B. Hechtman

Authors
  1. Seth L. Welles
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  2. David Shepro
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  3. Herbert B. Hechtman
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Additional information

Supported by NIH grants HL16714, HL33104, and GM24891.

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Welles, S.L., Shepro, D. & Hechtman, H.B. Eicosanoid modulation of stress fibers in cultured bovine aortic endothelial cells. Inflammation 9, 439–450 (1985). https://doi.org/10.1007/BF00916343

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