Elevation of chemotactic factor inactivator in alcoholic liver disease

R. A. Robbins, Rowen K Zetterman, T. J. Kendall, G. L. Gossman, H. P. Monsour, S. I. Rennard

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Abstract

Defective regulation of neutrophil chemotaxis occurs in patients with alcoholic liver disease. One potent mediator of neutrophil chemotaxis is the complement‐derived neutrophil chemoattractant, C5a, which can be inhibited by a serum protein, chemotactic factor inactivator. We hypothesized that chemotactic factor inactivator elevation might, in part, explain the defective neutrophil chemotaxis seen in patients with alcoholic hepatitis. To test this hypothesis, sera were collected from 22 patients with alcoholic hepatitis and 9 normal controls, and evaluated for the antigenic presence of chemotactic factor inactivator using an ELISA test. Chemotactic factor inactivator levels were found to be markedly elevated in patients with alcoholic hepatitis (162 ± 24 μg per ml) compared to normals (60 ± 3 μg per ml, p < 0.01). Subdividing the hepatitis patients revealed that the elevation of chemotactic factor inactivator was found to be greatest in those patients with mild alcoholic hepatitis (prothrombin time within normal limits and bilirubin ≤5 mg per dl, 256 ± 44 μg per ml, p < 0.001), while the group with the severest hepatic dysfunction (prolonged prothrombin time and bilirubin >5 mg per dl) did not differ significantly from controls (71 ± 11 μg/ml, p < 0.2). Importantly, the inhibition of C5a‐induced chemotactic activity by partially purified chemotactic factor inactivator correlated with antigenic amounts of chemotactic factor inactivator in serum (r = 0.63, p < 0.05). The C5a inhibitory activity in sera obtained from patients with alcoholic hepatitis coprecipitated with chemotactic factor inactivator when serum was precipitated by ammonium sulfate precipitation (45 to 64% saturation). Depleting chemotactic factor inactivator by affinity chromatography resulted in a major loss of the ability of this partially purified chemotactic factor inactivator to inhibit C5a‐induced chemotaxis (50 vs. 26% inhibition, p < 0.001), suggesting that chemotactic factor inactivator is a major inhibitor of C5a in these patients. These data suggest that elevations in chemotactic factor inactivator may explain impaired neutrophil chemotaxis in patients with alcoholic hepatitis.

Original languageEnglish (US)
Pages (from-to)872-877
Number of pages6
JournalHepatology
Volume7
Issue number5
DOIs
StatePublished - Jan 1 1987

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Alcoholic Liver Diseases
Alcoholic Hepatitis
Chemotaxis
Neutrophils
Serum
chemotactic factor inactivator
Aptitude
Chemotactic Factors
Ammonium Sulfate
Affinity Chromatography
Blood Proteins
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Hepatology

Cite this

Robbins, R. A., Zetterman, R. K., Kendall, T. J., Gossman, G. L., Monsour, H. P., & Rennard, S. I. (1987). Elevation of chemotactic factor inactivator in alcoholic liver disease. Hepatology, 7(5), 872-877. https://doi.org/10.1002/hep.1840070513

Elevation of chemotactic factor inactivator in alcoholic liver disease. / Robbins, R. A.; Zetterman, Rowen K; Kendall, T. J.; Gossman, G. L.; Monsour, H. P.; Rennard, S. I.

In: Hepatology, Vol. 7, No. 5, 01.01.1987, p. 872-877.

Research output: Contribution to journalArticle

Robbins, RA, Zetterman, RK, Kendall, TJ, Gossman, GL, Monsour, HP & Rennard, SI 1987, 'Elevation of chemotactic factor inactivator in alcoholic liver disease', Hepatology, vol. 7, no. 5, pp. 872-877. https://doi.org/10.1002/hep.1840070513
Robbins RA, Zetterman RK, Kendall TJ, Gossman GL, Monsour HP, Rennard SI. Elevation of chemotactic factor inactivator in alcoholic liver disease. Hepatology. 1987 Jan 1;7(5):872-877. https://doi.org/10.1002/hep.1840070513
Robbins, R. A. ; Zetterman, Rowen K ; Kendall, T. J. ; Gossman, G. L. ; Monsour, H. P. ; Rennard, S. I. / Elevation of chemotactic factor inactivator in alcoholic liver disease. In: Hepatology. 1987 ; Vol. 7, No. 5. pp. 872-877.
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abstract = "Defective regulation of neutrophil chemotaxis occurs in patients with alcoholic liver disease. One potent mediator of neutrophil chemotaxis is the complement‐derived neutrophil chemoattractant, C5a, which can be inhibited by a serum protein, chemotactic factor inactivator. We hypothesized that chemotactic factor inactivator elevation might, in part, explain the defective neutrophil chemotaxis seen in patients with alcoholic hepatitis. To test this hypothesis, sera were collected from 22 patients with alcoholic hepatitis and 9 normal controls, and evaluated for the antigenic presence of chemotactic factor inactivator using an ELISA test. Chemotactic factor inactivator levels were found to be markedly elevated in patients with alcoholic hepatitis (162 ± 24 μg per ml) compared to normals (60 ± 3 μg per ml, p < 0.01). Subdividing the hepatitis patients revealed that the elevation of chemotactic factor inactivator was found to be greatest in those patients with mild alcoholic hepatitis (prothrombin time within normal limits and bilirubin ≤5 mg per dl, 256 ± 44 μg per ml, p < 0.001), while the group with the severest hepatic dysfunction (prolonged prothrombin time and bilirubin >5 mg per dl) did not differ significantly from controls (71 ± 11 μg/ml, p < 0.2). Importantly, the inhibition of C5a‐induced chemotactic activity by partially purified chemotactic factor inactivator correlated with antigenic amounts of chemotactic factor inactivator in serum (r = 0.63, p < 0.05). The C5a inhibitory activity in sera obtained from patients with alcoholic hepatitis coprecipitated with chemotactic factor inactivator when serum was precipitated by ammonium sulfate precipitation (45 to 64{\%} saturation). Depleting chemotactic factor inactivator by affinity chromatography resulted in a major loss of the ability of this partially purified chemotactic factor inactivator to inhibit C5a‐induced chemotaxis (50 vs. 26{\%} inhibition, p < 0.001), suggesting that chemotactic factor inactivator is a major inhibitor of C5a in these patients. These data suggest that elevations in chemotactic factor inactivator may explain impaired neutrophil chemotaxis in patients with alcoholic hepatitis.",
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