Learning in the marine mollusk Aplysia has been associated with enhanced sensory function, expressed in mechanosensory neurons as (i) decreases in action potential threshold, accommodation, and afterhyperpolarization, and (ii) increases in action potential duration, afterdischarge, and synaptic transmission. These alterations also occur, with a delay, after sensory axons are injured under conditions in which synaptic transmission is severely reduced. The latency and specificity of injury-induced alterations indicate that induction signals are generated at the site of injury and conveyed centrally by axonal transport. Similarities in neuronal modifications support the hypothesis that some memory mechanisms evolved from mechanisms of injury-induced sensory compensation and repair.
Net ion transport by jejunum of rats immunized against Trichinella spiralis on challenge with parasite-derived antigen was measured in Ussing chambers as a rapidly expressed, biphasic rise and fall (phase I and II) in short-circuit current (delta Isc). This delta Isc is triggered by mucosal anaphylaxis. Our objective is to identify mast cell-derived substances that mediate the epithelial response. Antigenic challenge of sensitized jejunum caused the release of 5-hydroxytryptamine (5-HT), histamine, and prostaglandin E2 (PGE2). The antigen-induced phase I response was mimicked by exogenous 5-HT or histamine and blocked by pretreatment of tissue with 5-HT and histamine H1-antagonists; the phase II response was mimicked by exogenous PGE2 and blocked by an inhibitor of prostaglandin synthesis. Atropine and tetrodotoxin significantly blunted the phase I response as well as the delta Isc caused by exogenous 5-HT or histamine while only slightly reducing the phase II response and not affecting the delta Isc induced by PGE2. Results support the conclusion that 5-HT, histamine, and PGE2 mediate the antigen-induced change in Isc through direct and neurally mediated stimulation of jejunal epithelium.
We thank A. Clatworthy, M. Dulin, and P. Illich for comments on an earlier version of this article, J. Pastore for preparing the figures, and N. Karin for use of cell culture facilities.
This review highlights work that, within the past decade, transformed mucosal immunophysiology from a hypothetical concept to a fully recognized interdiscipline. The regulation of epithelial and smooth muscle functions by the mucosal immune system represents an exquisitely sensitive adaptation to local antigenic challenge. Furthermore, immunologic cells communicate with nerves via paracrine secretions to rapidly transduce antigenic signals into panmucosal changes in function. These local immunocyte-nerve interactions are modulated by the autonomic and central nervous systems. Because of the common mucosal immune system, antigen-induced changes similar to those occurring in the intestine and colon are predicted to occur in mucosa of all hollow organs. The drawing together of fields as diverse as medicine and agriculture underscores the scope of areas encompassed by immunophysiology. Newly acquired knowledge has positioned the field to advance rapidly in both basic and applied directions. Forces that will remodel the field in the next decade will be derived from public concerns about human health maintenance and the explosive and novel use of new research tools stemming from molecular biology. These forces will draw on and advance our knowledge in areas as diverse as vaccine development and prevention of allergic reactions to foods, bioengineered foods in particular.
The hypothesis that lactoferrin protects mice against lethal effects of bacterial lipopolysaccharide (LPS) is the subject of experimental investigations described in this article. Lipopolysaccharide is a powerful toxin produced by gram negative bacteria that when injected into humans or experimental animals reproduce many of the pathophysiologic and immune responses caused by live bacteria. Lactoferrin administered intraperitoneally 1 hr prior to injection of LPS significantly enhanced the survival of mice, reducing LPS-induced mortality from 83.3% to 16.7%. Changes in locomotor and other behavioral activities resulting from LPS injection were not present in mice treated with lactoferrin. Also, histological examination of intestine revealed remarkable resistance to injury produced by LPS if mice were pretreated with lactoferrin. Severe villus atrophy, edema and epithelial vacuolation were observed in LPS-treated animals but not in lactoferrin-treated counterparts. Electrophysiological parameters were used to assess secretory and absorptive functions in the small intestine. In mice treated with LPS, transmural electrical resistance was reduced and absorption of glucose was increased. Lactoferrin treatment had no significant influence on basal electrophysiological correlates of net ion secretion or glucose absorption nor on changes induced by LPS. Collectively, these results suggest that lactoferrin attenuates the lethal effect of LPS and modulates behavioral and histopathological sequela of endotoxemia.
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