Evidence for a Structural Requirement for the Aggregation of Platelets by Collagen

Abstract

A B S T R A C T This study investigates whether soluble collagen can initiate platelet aggregation or whether a higher degree of polymerization is required. Purified rat skin collagen was prepared in four states. Soluble monomeric collagen, containing 2 /hM calcium chloride, was maintained at 4°C until use. A previously uncharacterized form of collagen, soluble microfibrillar collagen, was prepared from monomeric collagen containing calcium chloride by allowing it to polymerize at 230 C. Viscometric and electron microscopic characterization of microfibrillar collagen indicated polymerization to ordered native filaments. Particulate native macrofibrillar collagen was prepared from monomeric collagen by allowing it to polymerize at 37°C in the absence of calcium. Particulate collagen, in which the fibers were randomly associated, was prepared by salt precipitation of calcium-free monomeric collagen. Microfibrillar and native macrofibrillar collagen initiated platelet aggregation, with a lag phase of approximately 60 s. Monomeric collagen initiated aggregation with a lag phase of approximately 180 s. The duration of the lag phase for platelet aggregation initiated by monomeric collagen was independent of the dose. Salt-precipitated particulate collagen did not initiate platelet aggregation. Agents which prolong the transition from monomeric collagen to fibrillar collagen (urea, arginine) retarded or prevented the aggregation of platelets by monomeric collagen. Sodium borohydride, which stabilizes the intraand intermolecular cross-links of collagen did not affect platelet aggregation. Penicillamine, which displaces the intermolecular cross-links and binds the intramolecular cross-links of collagen, did not prevent platelet aggregation. The data suggest that an architectural requirement exists for the initiation of self-perpetuating platelet ag-

The Role of Collagen Quaternary Structure in the Platelet:Collagen Interaction

“…Recently two other groups of investigators have arrived at conclusions similar to those presented here (29,30). Both groups used platelet aggregation rather than the release reaction as an index of the platelet: collagen interaction.…”

Platelet interaction with modified articular cartilage. Its possible relevance to joint repair.

“…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). To this should be added that, in vivo, the reactivity of a given connective tissue with platelets may not only be a reflection of the spacing and incidence of the active sites on the collagen molecule, but also of the type, concentration, and steric conformation of the surrounding mucopolysaccharides which may block these sites.…”

Lipoprotein (a) – An Overview

“…The adherence of platelets to the exposed connective tissue, preferably collagen, leads to aggregation followed by the release of ADP, 5-hydroxytryptamine and Ca 2+ from their dense granules, causing passing platelets to adhere to the primary clot [28].…”