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Peptides derived from C-reactive protein inhibit neutrophil alveolitis.

R M Heuertz, N Ahmed and R O Webster
J Immunol May 1, 1996, 156 (9) 3412-3417;
R M Heuertz
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N Ahmed
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R O Webster
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Abstract

C-reactive protein (CRP) is the classic acute phase reactant in humans, with serum levels elevated up to 1000-fold after the onset of inflammation. CRP inhibits chemotaxis of complement (C5a)-, LTB4-, IL-8-, and FMLP-stimulated neutrophils in vitro, and rabbits and transgenic mice with elevated serum CRP levels exhibit diminished neutrophil infiltration and vascular permeability in models of chemotactic factor-induced alveolitis. To evaluate the mechanism of CRP inhibition on chemoattractant-induced neutrophil inflammation in vivo, experiments were performed in mice infused with peptides of human CRP shown to inhibit C5a- and FMLP-stimulated neutrophil chemotaxis in vitro. After direct tracheal instillation of FMLP, mice previously injected via the retro-orbital plexus with CRP peptide 77-82 or 201-206 showed significant reductions (up to 90%) of neutrophils in the bronchoalveolar lavage fluid compared with vehicle-treated mice. Both CRP peptides also significantly (up to 55%) inhibited the increase in alveolar total protein levels. Control injections of native rabbit CRP (3 microM) inhibited neutrophil influx by 93% and protein leak by 55% in mice intratracheally instilled with FMLP. Despite similar levels of inhibition, approximately 10-fold more peptide by weight than native CRP was required. These data suggest that CRP degradation products at sites of tissue injury, in particular CRP peptides 77-82 and 201-206, are anti-inflammatory and can diminish lung injury by a reduction in neutrophil influx and protein leakage into alveoli following FMLP-induced inflammation.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 156, Issue 9
1 May 1996
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Peptides derived from C-reactive protein inhibit neutrophil alveolitis.
R M Heuertz, N Ahmed, R O Webster
The Journal of Immunology May 1, 1996, 156 (9) 3412-3417;

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Peptides derived from C-reactive protein inhibit neutrophil alveolitis.
R M Heuertz, N Ahmed, R O Webster
The Journal of Immunology May 1, 1996, 156 (9) 3412-3417;
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