Rabbits with elevated serum C-reactive protein exhibit diminished neutrophil infiltration and vascular permeability in C5a-induced alveolitis

R. M. Heuertz, C. A. Piquette, R. O. Webster

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

In previous studies, we have shown that C-reactive protein (CRP) inhibits chemotaxis of neutrophils to complement fragments in vitro. To evaluate the effect of CRP on C5a-induced inflammation in vivo, a rabbit model of alveolitis was used. Rabbits pretreated with subcutaneous injections of croton oil had serum CRP increase from undetectable levels to 270 ± 70 μg/ml 48 hours later. Rabbits were intubated and C5a des arg (10 μg/ml) instilled directly into the lungs via an endotracheal tube. Four to six hours later, the animals were killed and bronchoalveolar lavage performed. Rabbits pretreated with croton oil had significantly (P < 0.01) reduced C5a des arg- stimulated neutrophil infiltration (30 ± 5%) into alveolar air spaces compared to untreated rabbits (64 ± 9%). Increased numbers of total leukocytes in the alveolar washes coincided with increased neutrophil numbers whereas alveolar macrophages remained unchanged in all groups. Rabbits pretreated with croton oil also had a significant decrease (P < 0.05) in total protein (320 ± 50 μg/ml) in lavage fluid after C5a instillation compared with untreated animals (850 ± 140 μg/ml). In vitro, rabbit CRP (50 μg/ml) added to normal rabbit serum significantly (P < 0.05) inhibited chemotaxis of human neutrophils by 41%. Finally, direct intravenous pretreatment of rabbits with purified CRP also significantly reduced C5a- induced alveolitis. The CRP-C5a group had 33 ± 10% neutrophil infiltration, a significant (P < 0.01) reduction from the C5a group (71 ± 6%). The total protein content of the CRP-C5a rabbits was 986 ± 165 μg/ml in the lavage fluid, which was significantly (P < 0.05) lower than the C5a group (1645 ± 363 μg/ml). Therefore, CRP inhibits the development of neutrophil alveolitis and protein leakage in vivo and inhibits neutrophil chemotaxis in vitro. These data indicate that CRP offers a protective effect in neutrophil- mediated lung injury by reducing neutrophil influx and protein leak.

Original languageEnglish (US)
Pages (from-to)319-328
Number of pages10
JournalAmerican Journal of Pathology
Volume142
Issue number1
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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