Normal Chemotactic Migration of Polymorphonuclear Leukocytes Stimulated with Mononuclear-Derived Chemotactic Factor in Ulcerative Colitis

Abstract

The migration of polymorphonuclear leukocytes preincubated with autologous or heterologous serum was examined in 100 patients with untreated ulcerative colitis (UC) and in 100 age- and sex-matched healthy controls. The activity of complement-derived chemotactic factors and mononuclear-derived chemotactic factor (MDCF) was also investigated in the same group of patients. No significant difference was found in random and chemotactic migration of patients or control leukocytes preincubated in different concentrations (10, 50 and 100%) of autologous or heterologous serum. Defective chemotaxis of leukocytes stimulated with complement-derived chemotactic factors was found in UC and was more marked in patients in remission than with active UC independently of whether complement was activated by the alternative or the classical pathway. However, the random migration of neutrophils was enhanced in both groups of UC patients. The leukocytes of patients stimulated with MDCF (mononuclear cells were activated with lipopolysaccharide from Escherichia coli O55 :B5) show normal chemotaxis. Our data suggest an impairment of neutrophil receptors for complement-derived chemotactic factor in UC. The decreased response of neutrophils to these factors and normal response to MDCF suggest that the main way in which cells are attracted to the site of inflammation in UC may be a factor produced by stimulated mononuclear cells.

Increased expression of interleukin-8 mRNA in ulcerative colitis and Crohn's disease mucosa and epithelial cells

“…Indeed, a number of observations support a potential major role for neutrophils in the pathogenesis of UC. First, the ability of neutrophils to undergo chemotactic migration in UC has been shown to depend on the activity of the disease; i.e., chemotactic migration of neutrophils from UC patients was decreased in inactive colitis, but increased in active UC and markedly heightened in severe disease (33). Second, in both UC and CD patients, there is an enormously increased flux of neutrophils in vivo into the mucosa and then on into the intestinal lumen (34).…”

“…Second, in both UC and CD patients, there is an enormously increased flux of neutrophils in vivo into the mucosa and then on into the intestinal lumen (34). Third, neutrophil activation and migration are inhibited by drugs frequently used for the treatment of IBD, including 5-ASA, sulfasalazine, and prednisone (33,35).…”