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Modulation of the chemotactic properties of complement fragments C5a and C3 by the anti-inflammatory agent, SC-41930

  • Inflammatory Cells
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Abstract

Cleavage of the fifth component of complement yields C5a, a potent neutrophil (PMN) and eosinophil chemoattractant, and modulator of microvascular permeability. Similarly, but to a lesser degree, C3 increases vascular permeability and histamine release. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid), an orally-active antiinflammatory agent was tested in anin vivo model of dermal PMN chemotaxis induced by r-hu-C5a and hu-C3. Intradermal injection of C5a in the guinea pig resulted in a significant dose-dependent influx of PMNs at 4 hours as assessed by the dermal levels of myeloperoxidase (MPO). SC-41930 (20 mg/kg) given orally to guinea pigs with intradermal injections of 1 μg C5a significantly (p<0.001) reduced dermal MPO content. SC-41930 was less potent against C3, requiring 40 mg/kg to significantly reduce dermal MPO levels. Agents such as SC-41930, which nullify complement's proinflammatory properties, may well have therapeutic potential.

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Authors and Affiliations

  1. Gastrointestinal Diseases Research, Searle Research and Development, 4901 Searle Parkway Skokie, 60077, Skokie, II, USA

    D. J. Fretland, D. L. Widomski, C. P. Anglin & T. S. Gaginella

  2. Department of Pathology, Searle Research and Development, 4901 Searle Parkway Skokie, 60077, Skokie, II, USA

    S. Levin

Authors
  1. D. J. Fretland
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  2. D. L. Widomski
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  3. C. P. Anglin
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  4. S. Levin
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  5. T. S. Gaginella
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Fretland, D.J., Widomski, D.L., Anglin, C.P. et al. Modulation of the chemotactic properties of complement fragments C5a and C3 by the anti-inflammatory agent, SC-41930. Agents and Actions 34, 5–7 (1991). https://doi.org/10.1007/BF01993222

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  • DOI: https://doi.org/10.1007/BF01993222

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