Immune system control of rat and rabbit colonic electrolyte transport. Role of prostaglandins and enteric nervous system.

Abstract

The role of the immune system in controlling intestinal electrolyte transport was studied in rat and rabbit colon in Ussing chambers. A phagocyte stimulus, the chemotactic peptide FMLP, and a mast cell stimulus, sheep anti-rat IgE, caused a brief (< 10 min) increase in short-circuit current (Isc). Products of immune system activation, platelet-activating factor (PAF).and reactive oxygen species (ROS), caused a sustained, biphasic increase in the Isc. Ion replacement and flux studies indicated that these agonists stimulated electrogenic Cl secretion and inhibited neutral NaCI absorption; responses that were variably inhibited by the cyclooxygenase blockers indomethacin and piroxicam. Lesser degrees of inhibition by nordihydroguaiaretic acid could be accounted for by decreased prostaglandin synthesis rather than by lipoxygenase blockade. Tetrodotoxin, hexamethonium, and atropine also inhibited immune agonist-stimulated Isc, but had no effect on immune agonist-stimulated production of PGE2 or PGI2. These results indicate that immune system agonists alter intestinal epithelial electrolyte transport through release of cyclooxygenase products from cells in the lamina propria with at least 50% of the response being due to cyclooxygenase product activation of the enteric nervous system. The immune system, like the enteric nervous system and the endocrine system, may be a major regulating system for intestinal water and electrolyte transport in health and disease.

Role of platelet activating factor in the intestinal epithelial secretory and Chinese hamster ovary cell cytoskeletal responses to cholera toxin.

“…Error bars represent 1 SD. (18)(19)(20)(21). Although other submucosal cell types may also produce PAF, as has been suggested by Berschneider and Powell (29,30), our finding that T-84 cells can directly respond to cholera toxin with increased PAF production documents that human epithelial cells may serve as an autocrine source of PAF in response to cholera toxin.…”

“…Because platelet activating factor (PAP), recently identified as a secretagogue (18)(19)(20)(21), can also stimulate phospholipase A2 (22,23), thereby increasing the synthesis of prostaglandins, we sought to explore the potential role of PAF in the secretory and CHO cell responses to cholera toxin. 1% fetal bovine serum and studied as described previously (7).…”

PAR1-dependent and independent increases in COX-2 and PGE2 in human colonic myofibroblasts stimulated by thrombin

“…The induction of epithelial chloride secretion by elevated PGE 2 synthesis is a host defense mechanism (11) induced by the presence of bacterial products and allergens, thus preventing tissue invasion and injury (10,31). In these circumstances, the luminal bacteria and their products (as mimicked by LPS) induce an inflammatory response that includes increased vascular permeability (15,30).…”

“…Coculture studies indicate that the myofibroblast regulates epithelial cell chloride secretion by producing prostaglandin E 2 (PGE 2 ) (11) via cyclooxygenase (COX)-2 (25). In intestinal tissue, this regulation represents a rapidly activated host defense mechanism where PGE 2 -induced chloride secretion leads to water secretion that flushes away invading bacteria (10).…”

Platelet-Activating Factor Regulates Chloride Transport in Colonic Epithelial Cell Monolayers

“…The direct effect by PAF on airway epithelial cells has been demonstrated at micromolar concentrations and elicited from the mucosal side of the monolayers. The effect on intestinal transport has been thought to be mediated only indirectly via the stimulated production of mediators such as prostaglandins (12,21) and thromboxanes (13). The indirect effect of PAF on intestinal explants has only been observed from the serosal side at nanomolar concentrations.…”