Neutrophil modulation by Actinobacillus actinomycetemcomitans. I. Chemotaxis, surface receptor expression and F-actin polymerization.
Localized juvenile periodontitis is an early onset periodontitis, usually localized to molars and incisors. Patients usually present with decreased chemotaxis of systemic neutrophils (PMNs) and infection with Actinobacillus actinomycetemcomitans. The pathogenic mechanisms involved have not been clarified. The purpose of this study was to determine if an extract of A. actinomycetemcomitans could induce changes in PMN chemotaxis similar to those reported in LJP patients. It was demonstrated that the bacterial extract was chemotactic for neutrophils. When neutrophils were pre-incubated with the bacterial extract, chemotaxis toward zymosan-activated serum, FMLP and the bacterial extract was inhibited in two different chemotaxis assays (Boyden chamber and under-agarose). Bacterial extract had no effect on random migration in either assay. Pre-incubation with the extract induced increased expression of CD11b/CD18 (Mac-1), Gp110, and FMLP receptors and increased F-actin polymerization following FMLP or PMA stimulation compared to cells not treated with the extract. Treatment of the bacterial extract with proteinase K or phenol extraction reversed the PMN chemotaxis inhibition activity, but increased significantly the random migration of PMNs. Heating the bacterial extract to 56 degrees C had no effect on its activity. The component(s) in the bacterial extract that inhibits chemotaxis is therefore a protein(s), not sensitive to 56 degrees C, and is not endotoxin. This study suggests that A. actinomycetemcomitans may contribute to the pathogenesis of localized juvenile periodontitis by inhibiting chemotaxis. Interference with chemotaxis by A. actinomycetemcomitans, however, occurs through a mechanism other than inhibition of actin assembly, reduction of CD11b/CD18 or Gp110 expression, or blockage/downregulation of FMLP receptors.
Ashkenazi
M
M
Department of Periodontics, Dental Branch University of Texas Health Science Center, Houston.
White
R R
RR
Dennison
D K
DK
D000199:Actins / Q000378:metabolism; D016976:Aggregatibacter actinomycetemcomitans / Q000472:pathogenicity*; D010520:Aggressive Periodontitis / Q000276:immunology* / Q000382:microbiology; D015703:Antigens, CD / Q000378:metabolism; D001426:Bacterial Proteins; D001667:Binding, Competitive; D018821:CD18 Antigens; D002464:Cell Migration Inhibition; D002634:Chemotaxis, Leukocyte; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism*
D000199:Actins; D015703:Antigens, CD; D001426:Bacterial Proteins; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion; C030340:elastin microfibril interface located protein