The Gal/GalNAc reactive lectin of A. naeslundii WVU45 and the sialic acid reactive lectin of S. gordonii DLI recognized the same glycoprotein receptor on polymorphonuclear leukocytes (PMNs). Although the streptococcal lectin bound to the native sialylated receptor, binding of the actinomyces lectin required prior exposure of the appropriate saccharides by sialidase, an enzyme produced by these bacteria. Expression of this receptor was influenced by cell differentiation as indicated by enhanced binding of either bacteria during DMSO-induced differentiation of HL60 cells toward PMNs. This receptor was also subject to differentiation-dependent processing. The apparent molecular weight of the receptor on undifferentiated cells was 150 kD but shifted to that found on circulating PMNs (130 kD) following exposure of the HL60 cells to DMSO. Recognition of this PMN receptor by either of these bacterial lectins probably contributes to inflammation since both stimulated the production of superoxide anions as well as the release of PMN granule contents. Both bacteria were subsequently phagocytosed by the PMNs and the actinomyces, but not the streptococci, were killed. Six additional strains of S. gordonii were also phagocytosed by PMNs and, like DL1, two strains remained viable. Two strains were slightly susceptible to lectin-mediated destruction by PMNs but the remaining two strains were completely resistant. In a rat model of endocarditis the four strains that were resistant or only slightly susceptible to destruction by PMNs induced severe infection of previously traumatized aortic valves whereas the two strains that were destroyed by PMNs produced only mild infection. The production of endocarditis by these six strains of streptococci failed to correlate with aggregation of platelets, attachment to fibrin-platelet matrices or binding to fibronectin, laminin or fibrinogen. A major determinant of virulence for the production of endocarditis by this group of streptococci, therefore, appears to be resistance to lectin- mediated killing by PMNs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000557-03
Application #
3753578
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code