TY - JOUR
T1 - Rabbits with elevated serum C-reactive protein exhibit diminished neutrophil infiltration and vascular permeability in C5a-induced alveolitis
AU - Heuertz, Rita M.
AU - Piquette, Craig A.
AU - Webster, Robert O.
PY - 1993/1
Y1 - 1993/1
N2 - 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 (10μg/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 ± 50μg/ml) in lavage fluid after C5a instillation compared with untreated animals (850 ± 140μg/ml). In vitro, rabbit CRP (50μg/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.
AB - 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 (10μg/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 ± 50μg/ml) in lavage fluid after C5a instillation compared with untreated animals (850 ± 140μg/ml). In vitro, rabbit CRP (50μg/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.
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M3 - Article
C2 - 8424463
AN - SCOPUS:0027523923
SN - 0002-9440
VL - 142
SP - 319
EP - 328
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -