Collagens serve as an extracellular store of bioactive interleukin 2.
The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities. We show that interleukin 2 (IL-2), an important stimulator of T cell growth, preferentially binds to collagen types I, III, and VI and to a lesser degree to collagen types II, IV, and V, immobilized on polystyrene or nitrocellulose. These interactions are inhibited by denatured, single collagen chains or a subset of their cyanogen bromide peptides in a dose-dependent manner. Cross-inhibition experiments and ligand blotting of collagen-derived peptides point to a limited set of collagenous consensus sequences mediating the binding of IL-2. This interaction is saturable, with dissociation constants of approximately 10(-)(8) m, and estimated molar ratios of 4-6 molecules of IL-2 bound to one molecule of triple helical collagen. Furthermore, collagen-bound IL-2 stimulates proliferation of mouse lymphocytes. We conclude that its specific binding to the abundant interstitial collagens leads to a spatial pattern of bioavailable IL-2 which is dictated by the local organization of the collagenous extracellular matrix. This interaction may contribute to the particular phenotype of stromal lymphocytes and could be exploited for devising collagenous peptide analogues that modulate IL-2 bioactivity.
Somasundaram
R
R
Department of Gastroenterology and Hepatology, Klinikum Benjamin Franklin, Free University of Berlin, Berlin, Germany.
Ruehl
M
M
Tiling
N
N
Ackermann
R
R
Schmid
M
M
Riecken
E O
EO
Schuppan
D
D
D000818:Animals; D001665:Binding Sites; D003094:Collagen / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D016384:Consensus Sequence; D003488:Cyanogen Bromide; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D007376:Interleukin-2; D010446:Peptide Fragments; D011994:Recombinant Proteins; D003094:Collagen; D003488:Cyanogen Bromide