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Volume 272, Number 17, Issue of April 25, 1997 pp. 11044-11048
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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The Platelet Reactivity of Synthetic Peptides Based on the Collagen III Fragment 1(III)CB4
EVIDENCE FOR AN INTEGRIN ₂₁ RECOGNITION SITE INVOLVING RESIDUES 522-528 OF THE 1(III) COLLAGEN CHAIN

(Received for publication, October 23, 1996, and in revised form, January 3, 1997)

Laurence F. Morton , Anthony R. Peachey , C. Graham Knight , Richard W. Farndale and Michael J. Barnes

From the Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 4RN, United Kingdom and the  Department of Biochemistry, Cambridge University, Cambridge CB2 1QW, United Kingdom

The platelet-reactive collagen III-derived fragment 1(III)CB4 has been synthesized as seven overlapping peptides, each as a homotrimeric triple-helical species covalently linked at the C terminus. Additional Gly-Pro-Hyp triplets were introduced at each end of the peptide sequence to ensure a stable triple-helical conformation at 20 °C, the temperature at which cell reactivity was measured. A Cys-containing triplet was included at each end to allow intermolecular cross-linking. All seven peptides in triple-helical, cross-linked form were able to cause platelet aggregation. Peptide 6, the most reactive species, was more aggregatory than collagen fibers. Platelet adhesion occurred to all peptides immobilized on plastic in monomeric form. Adhesion was integrin ₂₁-independent except in the case of peptide 6, adhesion to which was partially reduced by anti-integrin ₂₁ monoclonal antibodies. The presence of an ₂₁ recognition site in peptide 6 was confirmed using HT 1080 cells, which express ₂₁ as their major or sole collagen receptor. HT 1080 adhesion to both peptide 6 and collagen was strongly inhibited by anti-integrin ₂₁ monoclonal antibodies. These cells did not adhere to any of the other peptides. Comparison of the structure of peptide 6 with that of adjacent peptides indicates that the sequence Gly-Gly-Pro-Hyp-Gly-Pro-Arg, residues 522-528 of the collagen 1(III) chain, represents the minimum structure required for the recognition of ₂₁. Our findings support the view that the collagen triple helix possesses an intrinsic platelet reactivity that can be expressed independently of integrin ₂₁ and the precise level of which is governed by the exact nature of the primary sequence. Sequences such as those recognizing ₂₁ may potentiate the activity, whereas others may have the opposite effect.

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