DEFECTIVE CHEMOTAXIS AND CALCIUM RESPONSE IN LOCALIZED JUVENILE PERIODONTITIS NEUTROPHILS

LoCALIZED JUVENILE PERIODONTITIS (LJP) is an early onset form of perio dontal disease characterized by unique localization to first molars an d incisors and a high prevalence of neutrophil abnormalities, particul arly chemotaxis. The intracellular transduction mechanisms that follow receptor-ligand coupling on the neutrophil surface and lead to chemot axis are not clearly established. Chemotaxis and phagocytosis are modu lated by a variety of receptors and involve several activation pathway s; the role of intracellular calcium as a presumptive second messenger and mediator of these events is well established. The putative effect or mechanisms for the chemotactic receptor of neutrophils also include the possible activation of a phospholipase, protein kinase C, methylt ransferase, or adenylate cyclase. In normal neutrophils, a phosphoinos itide pathway initiated by phospholipase C, which results in the activ ation of protein kinase C via diacylglycerol and the generation of IP3 , has been implicated. In order to better understand the stages of neu trophil transduction, fluorescent probes were used to monitor neutroph il calcium changes. Chlorotetracycline (CTC) was used as an indirect p robe of intracellular membrane-bound pool of calcium stores, and Quin- 2 was used to monitor cytosolic free calcium levels of FMLP stimulated normal and LJP neutrophils. The results indicate that the early phase of the calcium response affiliated with the release of intracellularl y sequestered calcium appears intact in LJP neutrophils, as the CTC fl uorescence changes were similar to control values. The second phase of the calcium response, associated with membrane channel activation and an influx of extracellular calcium, appeared compromised in the neutr ophils of the LJP population. These observations suggest an abnormalit y of signal transduction in LJP patients resulting in a decreased infl ux of extracellular calcium, perhaps due to failure in plasma membrane calcium channel activation or in an associated activation pathway.