Altered free cytosolic calcium changes and neutrophil chemotaxis in patients with juvenile periodontitis.
Nearly 70-75% of patients with localized juvenile periodontitis (JP) have abnormal polymorphonuclear leukocytic (PMN) chemotaxis. The objective of this study was to determine whether the lower chemotactic response in PMNs from JP patients is associated with a defect in intracellular signal transduction, as measured by stimulus-induced changes in free cytosolic calcium (Ca2+) mobilization. We report that peptide chemoattractants such as N-formyl-methionyl-leucyl-phenylalanine (fMLP) and the complement fragment C5a in direct comparative studies induced lower amounts of initial Ca2+ mobilization in PMNs from JP patients than healthy controls, as monitored by intracellular fura-2 fluorescence. The initial resting levels of free cytosolic Ca2+ in PMNs from JP patients and normal individuals were found to be similar. fMLP and C5a both mobilized Ca2+ in PMNs in a dose-dependent manner. Treatment of PMNs from 0.16 to 20 nM fMLP and 0.2 to 20 nM C5a resulted in elevated levels of free cytosolic Ca2+. However, above 20 nM fMLP and 5 nM C5a concentrations the extent of total Ca2+ mobilization did not differ significantly. Although fMLP and C5a caused Ca2+ mobilization in PMN cells from JP and healthy control subjects, fMLP stimulation induced higher levels of free cytosolic Ca2+ mobilization in PMN cells from healthy control subjects (141.29 +/- 25.55 nM/2 x 10(6) PMNs), than PMNs from JP patients (62.33 +/- 23.76 nM/2 x 10(6) PMNs). Similarly C5a induced higher levels of Ca2+ mobilization in PMNs from healthy control individuals (130.43 +/- 18.26 nM Ca2+/2 x 10(6) PMNs)O, when compared to JP patients (49.92 +/- 14.92 nM Ca2+/2 x 10(6) PMNs).(ABSTRACT TRUNCATED AT 250 WORDS)
Agarwal
S
S
Reynolds
M A
MA
Duckett
L D
LD
Suzuki
J B
JB
D000293:Adolescent; D000328:Adult; D010520:Aggressive Periodontitis / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D002648:Child; D003182:Complement C5 / Q000502:physiology; D015936:Complement C5a; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D015335:Molecular Probes; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010510:Periodontal Diseases / Q000503:physiopathology*
D003182:Complement C5; D015335:Molecular Probes; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D002118:Calcium