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.

The changes in short circuit current (electrogenic a-secretion) of rat colon brought about by xanthine/xanthine oxidase in the Ussing chamber were inhibited by catalase and diethyldithiocarbamate, but not by superoxide dismutase. These results, the reproduction of the response with glucose/glucose oxidase and with exogenous H202, and the lack of effect of preincubation with deferoxamine or thiourea implicate H202, and not 02 or OH, as the important reactive oxygen metabolite altering intestinal electrolyte transport. 1 mM H202 stimulated colonic PGE2 and PGI2 production 8-and 15-fold, respectively, inhibited neutral NaCl absorption, and stimulated biphasic electrogenic a secretion with little effect on enterocyte lactic dehydrogenase release, epithelial conductance, or histology. a-secretion was reduced by cyclooxygenase inhibition. Also, the Cl-secretion, but not the increase in prostaglandin production, was reduced by enteric nervous system blockade with tetrodotoxin, hexamethonium, or atropine. Thus, H202 appears to alter electrolyte transport by releasing prostaglandins that activate the enteric nervous system. The change in short circuit current in response to Iloprost, but not PGE2, was blocked by tetrodotoxin. Therefore, PGI2 may be the mediator of the H202 response. H202 produced in nontoxic concentrations in the inflamed gut could have significant physiologic effects on intestinal water and electrolyte transport. (J.

Keratoconus is characterized by stromal thinning and conical deformity of the cornea that affects a small but significant portion of the population. Although keratoconus has been well studied, endothehal changes have not been extensively investigated. We studied the endothelium of 14 keratoconus corneal buttons obtained over the past 6 years by penetrating keratoplasty using light microscopy, scanning electron microscopy and transmission electron microscopy. Observations were correlated with patient history. Corneas demonstrated: endothehal cell pleomorphism and polymegathism (6 corneas); endothehal cell degeneration (13), and evidence of anterior chamber inflammation (4). Patterns of endothehal damage were variable ranging from isolated cell membranolysis to denudement of Descemet’s membrane. Less damage was present at the apex of the cones than that observed in a circumferential pattern at the bases. In general the damage observed correlated with the severity and duration of the keratoconus with 9 years being the dividing time between mild and severe endothehal cell damage. These observations support other studies that implicate contact lens wear as a cause of pleomorphism and polymegathism in these patients. Endothehal cell alterations are likely a secondary event occurring due to mechanical stresses.

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