Complement receptor 1-related gene/protein y (Crry) is a murine membrane protein that regulates the activity of both classical and alternative complement pathways. We used a recombinant soluble form of Crry fused to the hinge, CH2, and CH3 domains of mouse IgG1 (Crry-Ig) to determine whether inhibition of complement activation prevents and/or reverses mesenteric ischemia/reperfusion-induced injury in mice. Mice were subjected to 30 min of ischemia, followed by 2 h of reperfusion. Crry-Ig was administered either 5 min before or 30 min after initiation of the reperfusion phase. Pretreatment with Crry-Ig reduced local intestinal mucosal injury and decreased generation of leukotriene B4 (LTB4). When given 30 min after the beginning of the reperfusion phase, Crry-Ig resulted in a decrease in ischemia/reperfusion-induced intestinal mucosal injury comparable to that occurring when it was given 5 min before initiation of the reperfusion phase. The beneficial effect of Crry-Ig administered 30 min after the initiation of reperfusion coincided with a decrease in PGE2 generation despite the fact that it did not prevent local infiltration of neutrophils and did not have a significant effect on LTB4 production. These data suggest that complement inhibition protects animals from reperfusion-induced intestinal damage even if administered as late as 30 min into reperfusion and that the mechanism of protection is independent of neutrophil infiltration or LTB4 inhibition.

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In order to test vaccines against enterotoxigenic Escherichia coli (ETEC)-10 CFU B7A or either dose of H10407. B7A had a shorter incubation period than H10407 (P ‫؍‬ 0.001) and caused milder illness; the mean diarrheal output after H10407 challenge was nearly twice that after B7A challenge (P ‫؍‬ 0.01). Females had more abdominal complaints, and males had a higher incidence of fever. Ciprofloxacin generally diminished or stopped symptoms and shedding by the second day of antibiotic treatment, but four subjects shed for one to four additional days. The immune responses to colonization factors CS6 and colonization factor antigen I (CFA/I) and to heat-labile toxin ( Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea is recognized frequently in individuals who travel in developing countries around the world (4,7,8,26,29,47) and is a major medical problem for military personnel deployed in these countries (26,44,45). Since strict personal hygiene and avoidance of local water and fresh and undercooked foods are recommendations with which travelers have difficulty complying, other means to reduce the ETEC attack rate must be considered. The use of short-term chemoprophylaxis and self-treatment for diarrhea are effective for travelers who are unwilling to accept even a short period of illness because of the serious impact it would have on their overall mission. However, the routine use of antimicrobial prophylaxis for the general traveler is not recommended because of the potential for associated adverse drug reactions and the potential to worsen the problem of antibiotic resistance of enteric bacteria (8,25,29,43,47). These factors make development of vaccines against ETEC a priority.

To investigate the characteristics of intestinal ion and fluid secretion induced by the adherent, effacing enteropathogenic Escherichia coli strain RDEC-1, we infected weanling rabbits with 10(7)-10(8) RDEC-1 organisms and then studied cecal ion transport under short-circuit conditions in Ussing chambers. Results in tissues with confluent adherent organisms were compared with those in uninfected ceca and in ceca stimulated with dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). The short-circuited cecum normally absorbed Na and Cl, secreted bicarbonate (as represented by the residual ion flux), and displayed a high rate of nondiffusional Na and Cl transport. RDEC-1 infection did not alter the short-circuit current (Isc), but it increased the conductance (Gt), decreased the potential difference (PD), abolished net Na absorption, and reversed Cl absorption to secretion. The changes in Na and Cl net fluxes may be explained by inhibition of a Na-Cl linked absorptive process. In contrast, DBcAMP significantly increased the Isc, PD, and Gt, decreased net Na flux, and abolished net Cl absorption by stimulating electrogenic Cl secretion. These results suggest that RDEC-1-induced changes in cecal ion transport are not mediated by cAMP. The reduction in Na-Cl linked absorption is consistent with anatomic changes in the apical surfaces of absorptive epithelial characteristic of effacing enteroadherence, whereas the increased conductance is consistent with tight junction disruption seen with RDEC-1 infection.

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