Collagen-Mediated Platelet Aggregation EFFECTS OF COLLAGEN MODIFICATION INVOLVING THE PROTEIN AND CARBOHYDRATE MOIETIES

Puett, David; Wasserman, Betty Kay; Ford, John D.; Cunningham, Leon W.

doi:10.1172/jci107440

Cited by 57 publications

(16 citation statements)

References 45 publications

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“…This concentration of gelatin also failed to alter the aggregation produced by a lower, suboptimal concentration of collagen. As reported (7,29) gelatin alone was incapable of initiating aggregation. Preimmune antiserum had no effect on adhesion.…”

Section: Methodssupporting

confidence: 58%

See 1 more Smart Citation

Fibronectin and the multiple interaction model for platelet-collagen adhesion.

Santoro¹,

Cunningham²

1979

Proc. Natl. Acad. Sci. U.S.A.

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A rapid, sensitive, and reproducible assay to determine the adhesion of platelets to collagen has been developed. Collagen fibers and adherent platelets are retained on polycarbonate membrane filters. Chemical modification of collagen by acetylation and of platelets by treatment with chymotrypsin markedly reduces adhesion. The role of fibronectin in the collagen-platelet interaction has been examined. Treatment of platelets with purified antibody or Fab' fragments to fibronectin only slightly reduces adhesion. Preincubation of platelets with high concentrations of gelatin reduces adhesion by only 22% but fails to inhibit aggregation. Thus, fibronectin has only a limited role in the adhesion qf platelets to collagen and is either not involved in the adhesion that leads to aggregation or is only one of several adhesion mechanisms, any of which alone can initiate aggregation.When the integrity of the vascular endothelium is destroyed, platelets rapidly aggregate at the site to form a hemostatic plug. Baumgartner (1) has demonstrated that fibrillar collagen is the most thrombogenic substance in vascular subendothelium. After first adhering to the collagen, the platelets undergo the release reaction in which ADP and other substances are released from secretory granules. In the presence of calcium these substances, especially ADP, result in formation of a platelet plug to close the vascular defect (2). The mechanism by which platelets adhere to collagen to initiate the hemostatic process is unknown.Jamieson and colleagues (3) proposed that formation of an enzyme-substrate complex between a platelet surface'collagen glucosyltransferase and galactosylhydroxylysine residues of collagen was the mechanism by which platelets adhere to collagen. Despite early support (4-6), studies in this (7,8) and other laboratories (9, 10) indicate that this mechanism is unlikely.It has been known for many years that the fibrillar form of collagen is required or, at least, is several orders of magnitude more effective in initiating aggregation than monomeric collagen (9, 11). Santoro and Cunningham (8) have recently proposed that adhesion of platelets to collagen and their subsequent aggregation result from-the interaction of multiple binding sites on the platelet surface, which may exhibit only modest affinity in the monovalent state for some'structural feature of the collagen molecule also multiply present in the collagen fibril. This concept is consistent with the similar capacities of the genetically distinct collagen types (8, 12, 13) In this paper we present a rapid assay for the determination of collagen-platelet adhesion and apply it to the examination of the possible role of fibronectin as the physiologic mediator of the collagen-platelet interaction. MATERIALS AND METHODSCollagen. Rat skin acid-soluble collagen was prepared by the method of Bornstein and Piez (20). Reconstituted native-type fibrils were prepared by dialysis of solutions of collagen in 3% acetic acid against 0.02 M Na2HPO4. Gelatin was prepared by heating...

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Section: Methodssupporting

confidence: 58%

“…Despite early support (4-6), studies in this (7,8) and other laboratories (9, 10) indicate that this mechanism is unlikely.…”

Section: Introductionmentioning

confidence: 90%

Fibronectin and the multiple interaction model for platelet-collagen adhesion.

Santoro¹,

Cunningham²

1979

Proc. Natl. Acad. Sci. U.S.A.

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“…Several dis- tinct forms of collagen are now known to exist and three have been isolated and characterized in some detail (10). All three have been reported to be effective in initiating platelet aggregation (7,22,23 The collagen types were also compared by adding solutions of the monomeric forms to platelet-rich plasma in the aggregometer. Under these conditions, as Jaffe and Deykin (2) and Muggli and Baumgartner (1) have shown for Type I collagen, a lag period is observed during which the monomeric collagen polymerizes to collagen fibrils which at some critical size and concentration can initiate platelet aggregation.…”

Section: Resultsmentioning

confidence: 99%

Collagen-mediated platelet aggregation. Evidence for multivalent interactions of intermediate specificity between collagen and platelets.

Santoro¹,

Cunningham²

1977

J. Clin. Invest.

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A B S T R A C T We have shown previously that periodate oxidation ofcollagen carbohydrate does not affect its ability to aggregate platelets. We now describe an additional characterization of periodate-modified collagen which demonstrates that collagen devoid of intact carbohydrate is fully capable of fibril formation, and we confirm its capacity to initiate platelet aggregation. Furthermore, we demonstrate that the platelet aggregating abilities of Types I, II, and III fibrillar collagen are quite similar despite differences in carbohydrate content and amino acid sequence. We also demonstrate that monomeric, pepsin-solubilized Type I human collagen is ineffective in inhibiting aggregation by preformed fibrils derived from the same molecule, thus establishing that the affinity of platelets for collagen depends upon prior polymerization of collagen. We interpret these and other findings to demonstrate that the hydroxylysyl glycoside regions of collagen are not highly specific sites involved in platelet-collagen interactions leading to "physiological" aggregation, and that the possibility must be considered that multiple interactions involving collagen sites of comparatively low structural specificity may be the initiating events in release of platelet ADP and the ensuing aggregation.

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“…The nature of the intermembranous bond between individual platelets or the mechanism whereby platelets adhere to collagen is therefore of great interest from many points of view. Yet, despite several attractive theories which have been advanced in recent years (5)(6)(7)(8)(9), in essence the process has remained poorly understood. On the basis of currently available evidence, it seems likely that a minimal structural unit consisting of rigidly spaced polar groups is necessary for platelet adhesion and subsequent aggregation to occur (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%