Elevation of chemotactic factor inactivator in alcoholic liver disease.
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 micrograms per ml) compared to normals (60 +/- 3 micrograms per ml, p less than 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 less than or equal to 5 mg per dl, 256 +/- 44 micrograms per ml, p less than 0.001), while the group with the severest hepatic dysfunction (prolonged prothrombin time and bilirubin greater than 5 mg per dl) did not differ significantly from controls (71 +/- 11 micrograms/ml, p less than 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 less than 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).(ABSTRACT TRUNCATED AT 250 WORDS)
D000626:Aminopeptidases / Q000097:blood*; D000941:Antigens / Q000032:analysis; D001663:Bilirubin / Q000097:blood; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D002846:Chromatography, Affinity; D003182:Complement C5 / Q000032:analysis; D015936:Complement C5a; D004797:Enzyme-Linked Immunosorbent Assay; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000145:classification / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008108:Liver Diseases, Alcoholic / Q000097:blood*; D009504:Neutrophils; D011517:Prothrombin Time
D000941:Antigens; D002630:Chemotactic Factors; D003182:Complement C5; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C010073:chemotactic factor inactivator; D015936:Complement C5a; D000626:Aminopeptidases; D001663:Bilirubin