Chemotactic peptides. Mechanisms, functions, and possible role in inflammatory bowel disease.

Abstract

An important component of host defenses is the ability of inflammatory cells to detect and respond to minute concentrations of chemoattractant substances. Chemotactic peptides elaborated by both bacteria and leukocytes are the focus of this review. These peptides induce directed migration of inflammatory cells towards their targets, and stimulate biological functions including degranulation, release of oxygen radicals, phagocytosis, and eicosanoid production. Among the released eicosanoids, leukotriene B4 potentiates the leukocyte response. As with other chemotactic factors, these functions are regulated partially through differential coupling to high- and low-affinity receptors and via calcium as the second messenger. Some chemotactic peptides are elaborated by normal colonic luminal bacteria. Recent evidence demonstrates that these peptides can produce mucosal inflammation in vivo. A possible mechanism for this effect involves abnormal colonic permeability in susceptible individuals that allows bacterial chemotactic peptides access to the mucosa where they may induce inflammation. Remaining questions include the mechanism by which the mucosal barrier is breached and the role of leukotrienes in the potentiation of colonic inflammation.