PORPHYROMONAS-GINGIVALIS FIMBRIAE USE BETA(2) INTEGRIN (CD11 CD18) ONMOUSE PERITONEAL-MACROPHAGES AS A CELLULAR RECEPTOR, AND THE CD18 BETA-CHAIN PLAYS A FUNCTIONAL-ROLE IN FIMBRIAL SIGNALING/

In this study, we demonstrate that Porphyromonas gingivalis fimbriae u se molecules of beta(2) integrin (CD11/CD18) on mouse peritoneal macro phages as cellular receptors and also show that the beta chain (CD18) may play a functional role in signalling for the fimbria-induced expre ssion of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alph a (TNF-alpha) genes in the cells, Using a binding assay with I-125-lab eled fimbriae, we observed that fimbrial binding to the macrophages wa s inhibited by treatment with CD11a, CD11c, CD11c, or CD18 antibody bu t not by that with CD29 antibody. Western blot assays showed that the fimbriae bound to molecules of beta(2) integrin (CD11/CD18) on the mac rophages. Furthermore, Northern blot analyses showed that the fimbria- induced expression of IL-1 beta and TNF-alpha genes in the cells was i nhibited strongly by CD18 antibody treatment and slightly by CD11a, CD 11b, or CD11c antibody treatment. Interestingly, intracellular adhesio n molecule 1 (ICAM-1), a ligand of CD11/CD18, inhibited fimbrial bindi ng to the cells in a dose-dependent manner. Pn addition, ICAM-1 clearl y inhibited the fimbria-induced expression of IL-1 beta and TNF-alpha genes in the cells.However, such inhibitory action was not observed wi th lamminin treatment. These results suggest the importance of beta(2) integrin (CD11/CD18) as a cellular receptor of P. gingivalis fimbriae in the initiation stage of the pathogenic mechanism of the organism i n periodontal disease.