Polymorphonuclear leukocytes (PMNs) are the infantry of the cellular host defense system. In response to infections PMNs exhibit an increase in a sequence of cell functions which include: adhesion, chemotaxis, phagocytosis, degranulation, and ultimately bacterial killing. The first four of these responses involve cell motility, and therefore depend on continued, orderly, long-term reorganizations of the actin cytoskeleton. Accumulating data indicate that receptor-ligand interactions initiate these cellular responses. Furthermore, the very early events following receptor-ligand interaction include an immediate, rapid, transient, alteration in the actin cytoskeleton and intracellular pH. In separate but related literature, clinical data indicate that anaerobic bacteria which are thought to cause periodonatal infections release short chain fatty acids. (SCFA) into their environment. These SCFA have been shown to inhibit PMN motile functions. We are therefore interested in answering the following molecular questions: 1. Do SCFAs alter the PMN actin cytoskeleton? 2. Do SCFAs alter the internal pH of the PMN? and 3. Do SCFAs alter PMN chemotactic peptide receptors? If the results of the proposed work indicate that the SCFAs do have a deleterious effect on PMNs, several additional questions will be of great clinical interest: What SCFAs are present in sites with active periodontitis? What is the effect of SCFA on other cells of the periodontium? and finally, Can bacterial cells be engineered which have reduced SCFA production?
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