The inhibitory complex of human alpha 1-proteinase inhibitor and human leukocyte elastase is a neutrophil chemoattractant.

An inhibitor-proteinase complex consisting of human alpha 1-PI and human leukocyte elastase is chemotactic for human neutrophils. The chemotactic activity is optimal at 1 nM and is associated only with the alpha 1-PI portion of the complex. Neither HLE in the complex, free HLE, nor native alpha 1-PI possesses chemotactic activity for human neutrophils. alpha 1-PI in complex is hydrolyzed at the Met-358-Ser-359 bond. The chemotactic activity is associated with the Mr 4,200 fragment of alpha 1-PI that has Ser-359 as its NH2 terminus. The region of the HLE-alpha 1-PI complex that stimulates chemotaxis appears to be the same as that of the Mr 4,200 fragment generated by hydrolysis of the Pro-357-Met-358 bond during proteolytic inactivation of alpha 1-PI. The data suggest the presence of a neutrophil surface receptor bound by alpha 1-PI after the formation of a complex with HLE or after proteolytic degradation. This receptor may play a role in clearance of these modified alpha 1-PI molecules.

Alpha 1-proteinase inhibitor is a neutrophil chemoattractant after proteolytic inactivation by macrophage elastase.

Mouse macrophage elastase, a metalloproteinase, catalytically inactivates human alpha 1-proteinase inhibitor (alpha 1-PI) by attacking a single peptide bond between Pro357 and Met358, resulting in Mr = 4,200 and 47,800 fragments. We show here that this proteolytically inactivated alpha 1-PI is a potent chemotactic factor for human neutrophils at a concentration of 1 nM. The chemotactic response is equivalent to that elicited by formyl-methionyl-leucyl-phenylalanine. Native alpha 1-PI does not stimulate chemotaxis. Purification of the two fragments of alpha 1-PI that result from proteolysis by macrophage elastase indicated that the Mr = 4,200 fragment is responsible for the chemotactic activity. However, the two proteolysis fragments do not dissociate from each other under physiologic conditions. Therefore, the ability of proteolytically inactivated alpha 1-PI to act as a mediator of inflammation is due to rearrangement of the alpha 1-PI molecule rather than to release of a cleavage fragment.

Neural and behavioral responsivity to ethyl alcohol as a tastant.

Three experiments were designed to study the sensory properties of ethyl alcohol (EtOH) in the rat. In Experiment 1, a conditioned taste aversion (CTA) was produced to 3%, 6% or 9% EtOH. None of these aversions generalized to any of the 4 basic tastants. However, rats in the 6% and 9% EtOH groups did generalize the CTA to a mixture of sucrose-QHCl but not to a mixture of NaCl-HCl. In Experiment 2, a CTA was produced to 6% EtOH and animals were then tested with all 6 combinations of the basic tastants. The CTA was found to generalize significantly to sucrose-QHCl and marginally to sucrose-HCl. In Experiment 3, single unit responses to gustatory stimuli were recorded in the nucleus of the tractus solitarius. Solutions of NaCl, HCl, sucrose, QHCl, 6% and 9% EtOH were bathed over the rostral tongue through a plastic flow chamber. Approximately half of the units responded to 9% EtOH. Analysis of the across-unit patterns of response revealed a weak relationship between responses to EtOh and sucrose in the first 1.0 sec of response.

Flavor-illness aversions: potentiation of odor by taste with toxin but not shock in rats.

Potentiation of odor by taste in rats was tested in a variety of situations. In three experiments, almond odor and saccharin taste were presented either as a single conditioned stimulus (CS) or as a compound CS and followed by either toxic lithium chloride or footshock. Extinction tests with the almond and saccharin components were then given. In single CS-toxin experiments, taste was more effective than odor, and after compound conditioning, the taste component potentiated the odor component. Conversely, in single CS-shock experiments, odor was more effective than taste, and after compound conditioning, no potentiation was observed. Rather, interference effects were observed. In Experiments 1 and 2, the addition of taste disrupted odor CS-shock conditioning, and in Experiment 3, odor interfered with taste CS-shock conditioning. Visceral feedback is apparently a necessary unconditioned stimulus for the potentiation of odor by taste. These data support the neural convergence and gating hypothesis of flavor aversion conditioning.