Inhibition of leucocyte adhesion molecule upregulation by tumor necrosis factor alpha: a novel mechanism of action of sulphasalazine.
The effects of the cytokine tumour necrosis factor alpha and the calcium ionophore A23187 upon CD11a, CD11b, CD11c and CD18 leucocyte membrane expression was analysed in whole blood using monoclonal antibodies and flow cytometry. Both agents significantly increased the density of CD11b/CD18 membrane expression on monocytes and granulocytes, but had no effects on adhesion molecule expression on lymphocytes. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA) and sulphapyridine upon adhesion molecule upregulation were then examined; 10(-3) and 10(-4) M sulphasalazine and 5-ASA significantly reduced tumour necrosis factor alpha induced CD11b/CD18 upregulation on monocytes and granulocytes but had no effects upon A23187 mediated upregulation. Sulphapyridine was inactive. These results suggest that sulphasalazine and 5-ASA may interfere with mechanisms of leucocyte recruitment in inflammatory bowel disease.
Greenfield
S M
SM
Gastrointestinal Laboratory, Rayne Institute, St Thomas' Hospital, London.
Hamblin
A S
AS
Shakoor
Z S
ZS
Teare
J P
JP
Punchard
N A
NA
Thompson
R P
RP
D000328:Adult; D015703:Antigens, CD / Q000032:analysis / Q000187:drug effects*; D018845:CD11 Antigens; D018821:CD18 Antigens; D000001:Calcimycin / Q000494:pharmacology; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D012460:Sulfasalazine / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D012460:Sulfasalazine