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Defective Chemotaxis and Calcium Response in Localized Juvenile Periodontitis Neutrophils
Author(s) -
Daniel Michael A.,
McDonald Georgia,
Offenbacher Steven,
Van Dyke Thomas E.
Publication year - 1993
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.1993.64.7.617
Subject(s) - chemotaxis , biology , microbiology and biotechnology , second messenger system , calcium , calcium in biology , signal transduction , phospholipase c , calcium signaling , receptor , intracellular , biochemistry , medicine
L ocalized juvenile periodontitis (ljp) is an early onset form of periodontal disease characterized by unique localization to first molars and incisors and a high prevalence of neutrophil abnormalities, particularly chemotaxis. The intracellular transduction mechanisms that follow receptor‐ligand coupling on the neutrophil surface and lead to chemotaxis are not clearly established. Chemotaxis and phagocytosis are modulated by a variety of receptors and involve several activation pathways; the role of intracellular calcium as a presumptive second messenger and mediator of these events is well established. The putative effector mechanisms for the chemotactic receptor of neutrophils also include the possible activation of a phospholipase, protein kinase C, methyltransferase, or adenylate cyclase. In normal neutrophils, a phosphoinositide pathway initiated by phospholipase C, which results in the activation of protein kinase C via diacylglycerol and the generation of IP 3 , has been implicated. In order to better understand the stages of neutrophil transduction, fluorescent probes were used to monitor neutrophil calcium changes. Chlorotetracycline (CTC) was used as an indirect probe 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 intracellularly sequestered calcium appears intact in LIP neutrophils, as the CTC fluorescence 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 neutrophils of the LJP population. These observations suggest an abnormality of signal transduction in LJP patients resulting in a decreased influx of extracellular calcium, perhaps due to failure in plasma membrane calcium channel activation or in an associated activation pathway. J Periodontol 1993; 64:617–621 .