Increase in platelet non-integrin type I collagen receptor in patients with systemic sclerosis.

Abstract

Microvascular injury is one of the major pathogenetic processes involved in systemic sclerosis (SSc). Interaction of the platelet types I and III collagen receptors with their respective ligand in the exposed subendothelial stroma as a result of ongoing microvascular injury in SSc patients results in platelet activation and aggregation with the release of mediators, which contribute to vascular damage and inflammation. We have found that there is a twofold increase in radiolabeled type I collagen binding to washed platelets from patients with SSc compared to platelets obtained from normal volunteers. Western blot analyses showed that the non-integrin platelet type I collagen receptor protein (65 kDa) is increased dramatically in lysates of platelet from patients with SSc. However, the integrin (alpha(2)beta(1)) and other non-integrin receptors such as glycoprotein VI, glycoprotein IV, and the platelet receptor for type III collagen remain unchanged. In addition, platelet lysates from rheumatic disease controls (rheumatoid arthritis, osteoarthritis, gout, and systemic lupus erythematosus) do not show any significant increases. There is no nitrotyrosylation on 65 kDa in patients with SSc compared to controls, suggesting this might also contribute to binding of CI to the 65-kDa CIR. These results suggest that there is a specific increase in the number of platelet type I collagen receptors in SSc patient's platelets. In addition, the activity of nitric oxide synthase is decreased in patients' platelet lysates compared to controls. The increase in platelet expression of the 65-kDa non-integrin platelet type I collagen receptor may explain the enhanced aggregation of platelets from patients with SSc to CI in vitro and microvascular thrombosis in the disease in vivo.

• Authors: Thomas M Chiang, Hiroshi Takayama, Arnold E Postlethwaite
• Journal: Thrombosis research (Thromb Res) Vol. 117 Issue 3 Pg. 299-306 ( 2006) ISSN: 0049-3848 [Print] United States
• PMID: 16378833 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Collagen Type I
• Integrin alpha2beta1
• Ligands
• Platelet Membrane Glycoproteins
• Receptors, Collagen
• type I collagen receptor
• Nitric Oxide Synthase

Topics

• Adult
• Blood Platelets (metabolism)
• Blotting, Western
• Collagen Type I (chemistry)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Integrin alpha2beta1
• Kinetics
• Ligands
• Male
• Microcirculation
• Middle Aged
• Nitric Oxide Synthase (metabolism)
• Platelet Activation
• Platelet Aggregation
• Platelet Membrane Glycoproteins (chemistry)
• Protein Binding
• Receptors, Collagen (biosynthesis, blood)
• Scleroderma, Systemic (metabolism, pathology)
• Time Factors