Modulation of neutrophil function by novel colonic factors: possible role in the pathophysiology of ulcerative colitis.
Tissue damage in acute ulcerative colitis (UC) may be triggered by neutrophils (PMNs) and their inflammatory mediators such as reactive oxygen species (ROS). Because circulating PMNs appeared normal in subjects with UC, we hypothesized that the critical abnormality that attracts and activates PMNs in UC is a local colonic factor. Accordingly, the colonic milieu was sampled by using in vivo rectal dialysis (mol wt < or = 12 kd). Normal PMNs were exposed in vitro to rectal dialysates (RD) from control subjects (cRD) or subjects with active UC (aRD) or inactive UC (IRD). PMN-derived ROS were measured by chemiluminescence. cRD did not increase ROS production by unstimulated PMNs; aRD significantly and concentration-dependently increased ROS; IRD gave intermediate results. cRD inhibited the PMN-stimulating effects of both the bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA). aRD and IRD blunted the effect of fMLP and PMA significantly less than did cRD. Rectal dialysates from 44% of subjects with active UC exaggerated the fMLP effect, whereas potentiation occurred for only 13% of cRDs and 18% of iRDs. cRD preconditioned with either activated or nonactivated PMNs was not significantly different than unconditioned cRD. We thus infer the existence of colonic factors in UC that (1) can trigger PMNs to produce ROS and (2) have a proinflammatory modulatory effect on bacterial peptide-induced, PMN-mediated ROS production, thereby initiating or perpetuating inflammation and eventually causing tissue damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Kazi
N
N
Department of Medicine, School of Medicine, Loyola University at Chicago, Maywood, IL 60153, USA.
Fields
J Z
JZ
Sedghi
S
S
Kottapalli
V
V
Eiznhamer
D
D
Winship
D
D
Keshavarzian
A
A
D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000503:physiopathology*; D003106:Colon / Q000378:metabolism*; D003956:Dialysis; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008165:Luminol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D012007:Rectum; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D009240:N-Formylmethionine Leucyl-Phenylalanine; D008165:Luminol; D013755:Tetradecanoylphorbol Acetate