scholarly journals Interaction of Fimbriae of Haemophilus influenzae Type B with Heparin-Binding Extracellular Matrix Proteins

2000 ◽  
Vol 68 (10) ◽  
pp. 5696-5701 ◽  
Author(s):  
Ritva Virkola ◽  
Mirko Brummer ◽  
Heikki Rauvala ◽  
Loek van Alphen ◽  
Timo K. Korhonen
Keyword(s):  
Extracellular Matrix ◽  
Haemophilus Influenzae ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Haemophilus Influenzae Type ◽  
Heparin Binding ◽  
Type B ◽  
Binding Domains ◽  
Human Fibronectin ◽  
High Concentrations

ABSTRACT The interaction of the fimbriae of Haemophilus influenzae type b (Hib) with two heparin-binding extracellular matrix proteins, human fibronectin (Fn) and heparin-binding growth-associated molecule (HB-GAM) from mouse, were studied. The fimbriated Hib strain 770235 fim+, as well as the recombinant strainE. coli HB101(pMH140), which expressed Hib fimbriae, adhered strongly to Fn and HB-GAM immobilized on glass. Purified Hib fimbriae bound to Fn and HB-GAM, and within the Fn molecule, the binding was localized to the N-terminal 30,000-molecular-weight (30K) and 40K fragments, which contain heparin-binding domains I and II, respectively. Fimbrial binding to Fn, HB-GAM, and the 30K and the 40K fragments was inhibited by high concentrations of heparin. The results show that fimbriae of Hib interact with heparin-binding extracellular matrix proteins. The nonfimbriated Hib strain 770235 fim− exhibited a low level of adherence to Fn but did not react with HB-GAM, indicating that Hib strains also possess a fimbria-independent mechanism to interact with Fn.

scholarly journals The Haemophilus influenzae Hap Autotransporter Binds to Fibronectin, Laminin, and Collagen IV

2002 ◽  
Vol 70 (9) ◽  
pp. 4902-4907 ◽  
Author(s):  
Doran L. Fink ◽  
Bruce A. Green ◽  
Joseph W. St. Geme
Keyword(s):  
Extracellular Matrix ◽  
Respiratory Tract ◽  
Haemophilus Influenzae ◽  
Extracellular Matrix Proteins ◽  
Collagen Iv ◽  
Binding Domain ◽  
Matrix Proteins ◽  
Heparin Binding ◽  
Upper Respiratory Tract ◽  
Passenger Domain

ABSTRACT Nontypeable Haemophilus influenzae (NTHI) initiates infection by colonizing the upper respiratory tract mucosa. NTHI disease frequently occurs in the context of respiratory tract inflammation, where organisms encounter damaged epithelium and exposed basement membrane. In this study, we examined interactions between the H. influenzae Hap adhesin and selected extracellular matrix proteins. Hap is an autotransporter protein that undergoes autoproteolytic cleavage, with release of the adhesive passenger domain, Haps, from the bacterial cell surface. We found that Hap promotes bacterial adherence to purified fibronectin, laminin, and collagen IV and that Hap-mediated adherence is enhanced by inhibition of autoproteolysis. Adherence is inhibited by pretreatment of bacteria with a polyclonal antiserum recognizing Haps. Purified Haps binds with high affinity to fibronectin, laminin, and collagen IV but not to collagen II. Binding of Haps to fibronectin involves interaction with the 45-kDa gelatin-binding domain but not the 30-kDa heparin-binding domain of fibronectin. Taken together, these observations suggest that interactions between Hap and extracellular matrix proteins may play an important role in NTHI colonization of the respiratory tract.

scholarly journals Glycoprotein IV-independent adhesion of sickle red blood cells to immobilized thrombospondin under flow conditions

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4862-4870 ◽  
Author(s):  
CC Joneckis ◽  
DD Shock ◽  
ML Cunningham ◽  
EP Orringer ◽  
LV Parise
Keyword(s):  
Extracellular Matrix ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Vascular Occlusion ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Flow Conditions ◽  
Adhesion Receptors ◽  
Binding Domains ◽  
Adhesive Site

The abnormal adherence of red blood cells (RBC to the blood vessel wall is believed to contribute to the vascular occlusion observed in patients with sickle call anemia. The cell adhesion receptors GPIV (CD36) and integrin alpha 4 beta 1 (CD49d/CD29) were previously identified on circulating sickle reticulocytes, and shown to mediate sickle RBC adhesion to the endothelium. The presence of damaged endothelium in these patients suggests that exposed extracellular matrix proteins could provide a potential substrate for sickle RBC adhesion. To determine whether RBC adhesion receptors could mediate adhesion to extracellular matrix proteins, we tested their ability to adhere to a variety of immobilized, purified proteins under flow conditions. Neither sickle nor normal RBC adhered to fibronectin, vitronectin, fibrinogen, or collagen. In contrast, we observed substantial adhesion of sickle but not normal RBC to thrombospondin (TSP). The adhesion was not inhibited with known antagonists of the GPIV-TSP interaction, nor by inhibitors of several other known binding domains in TSP. Moreover, the adhesion was resistant to inhibition by soluble TSP, suggesting that immobilization of TSP exposes an adhesive site that is cryptic on TSP in solution. However, the glycosaminoglycans, chondroitin sulfate A, and dextran sulfate were potent inhibitors of this adhesion. These results suggest that a mechanism distinct from GPIV is responsible for sickle RBC adhesion to immobilized TSP under flow conditions.

scholarly journals Chromosomal Expression of the Haemophilus influenzae Hap Autotransporter Allows Fine-Tuned Regulation of Adhesive Potential via Inhibition of Intermolecular Autoproteolysis

2003 ◽  
Vol 185 (5) ◽  
pp. 1608-1615 ◽  
Author(s):  
Doran L. Fink ◽  
Joseph W. St. Geme
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Haemophilus Influenzae ◽  
Critical Role ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Passenger Domain ◽  
Respiratory Epithelial Cells ◽  
Bacterial Aggregation ◽  
Respiratory Epithelial

ABSTRACT The Haemophilus influenzae Hap autotransporter is a nonpilus adhesin that promotes adherence to respiratory epithelial cells and selected extracellular matrix proteins and facilitates bacterial aggregation and microcolony formation. Hap consists of a 45-kDa outer membrane translocator domain called Hapβ and a 110-kDa extracellular passenger domain called HapS. All adhesive activity resides within HapS, which also contains protease activity and directs its own secretion from the bacterial cell surface via intermolecular autoproteolysis. In the present study, we sought to determine the relationship between the magnitude of Hap expression, the efficiency of Hap autoproteolysis, and the level of Hap-mediated adherence and aggregation. We found that a minimum threshold of Hap precursor was required for autoproteolysis and that this threshold approximated expression of Hap from a chromosomal allele, as occurs in H. influenzae clinical isolates. Chromosomal expression of wild-type Hap was sufficient to promote significant adherence to epithelial cells and extracellular matrix proteins, and adherence was enhanced substantially by inhibition of autoproteolysis. In contrast, chromosomal expression of Hap was sufficient to promote bacterial aggregation only when autoproteolysis was inhibited, indicating that the threshold for Hap-mediated aggregation is above the threshold for autoproteolysis. These results highlight the critical role of autoproteolysis and an intermolecular mechanism of cleavage in controlling the diverse adhesive activities of Hap.

Extracellular matrix proteins control the growth of cerebellar medulloblastoma cells

2004 ◽  
Vol 216 (03) ◽  
Author(s):  
U Schüller ◽  
W Hartmann ◽  
A Koch ◽  
K Schilling ◽  
OD Wiestler ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Cerebellar Medulloblastoma
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