Interferon-alpha receptor expression and regulation in chronic hepatitis B virus infection.
Interferon-alpha elicits antiviral and immunoregulatory activities by binding to specific receptors on the cell surface. In this study, binding characteristics of interferon-alpha to peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection were studied using radioiodinated recombinant interferon-alpha 2b to determine interferon-alpha receptor numbers and dissociation constants. A single class of interferon-alpha receptor was demonstrated on peripheral blood mononuclear cells and mononuclear subsets. Peripheral blood mononuclear cells from patients with chronic hepatitis B virus infection (n = 20) and controls (n = 16) expressed a similar number of interferon-alpha receptors (484 +/- 175 vs. 511 +/- 168 sites/cell respectively, p = NS) with a similar dissociation constant (dissociation constant approximately 0.2 to 0.7 nmol/L). Expression of interferon-alpha receptors was similar in monocyte-enriched and lymphocyte-enriched fractions in both groups. Similar changes were observed in patients receiving alpha-interferon therapy. There was no correlation between interferon-alpha receptors expression and serum transaminase, serum HBsAg, serum HBV DNA, liver histological findings or the response to interferon-alpha therapy. After incubation of lymphocytes in vitro with interferon-alpha 2b (10 to 1,000 U/ml), interferon-alpha receptors number dropped by 42% to 80%, but this was associated with an increase in binding affinity (dissociation constant approximately 0.05 to 0.15 nmol/L) in both patients and controls. There was significant delay in the initial phase of receptor recovery in the patients with chronic hepatitis B virus infection compared with normal controls (days 1 and 2, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Lau
J Y
JY
Liver Unit, King's College Hospital, London, United Kingdom.
Sheron
N
N
Morris
A G
AG
Bomford
A B
AB
Alexander
G J
GJ
Williams
R
R
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006509:Hepatitis B / Q000097:blood* / Q000382:microbiology; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011971:Receptors, Immunologic / Q000097:blood*; D017471:Receptors, Interferon; D011994:Recombinant Proteins
D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins