Nonimmune lymphocyte-macrophage interaction. II. Evidence that the interaction involves sulfated polysaccharide recognition.

This paper describes attempts to determine the molecular basis of the nonimmune interaction between lymphocytes and macrophages. Initial studies revealed that the interaction could be inhibited by simple sugars, six out of the thirty-five tested being inhibitory. Furthermore, the majority of the inhibitory sugars were charged and subsequent studies revealed that some sulfated polysaccharides, notably kappa-carrageenan, were potent inhibitors of the interaction. Further experiments revealed that the lymphocyte-macrophage interaction was indeed mediated by kappa-carrageenan-specific receptors on lymphocytes. The results supporting such a conclusion were as follows: When the interacting cells were preincubated with kappa-carrageenan, it was found that kappa-carrageenan exerted its inhibitory effect at the lymphocyte rather than the macrophage level. Separation of splenocytes into kappa-carrageenan-binding and -nonbinding subpopulations resulted in a corresponding enrichment and depletion of lymphocytes that reacted with macrophages. Lymphocytes were found to express kappa-carrageenan-reactive molecules, these molecules being detected on the surface of lymphocytes by rosetting and in detergent lysates as hemagglutinins. Furthermore, the polyanion specificity of these kappa-carrageenan-specific receptors/hemagglutinins closely resembled the specificity of inhibition of the lymphocyte-macrophage interaction. Pronase-resistant material in macrophage, but not lymphocyte lysates, effectively inhibited both the lymphocyte-macrophage interaction and the recognition of kappa-carrageenan by lymphocytes, suggesting that a kappa-carrageenan-like structure is expressed by macrophages.