Leukocyte integrins αLβ2, αMβ2 and αXβ2 as collagen receptors--receptor activation and recognition of GFOGER motif.

Integrins αLβ2, αMβ2 and αXβ2 are expressed on leukocytes. Their primary ligands are counter transmembrane receptors or plasma proteins, such as intercellular cell adhesion molecule-1 (ICAM-1) or components of complement system (iC3b, iC4b), respectively. Function blocking antibodies for these integrins may also reduce cell adhesion to collagens. To make the first systematical comparison of human α(L)β2, α(M)β2 and α(X)β2 as collagen receptors, we produced the corresponding integrin αI domains both in wild-type and activated form and measured their binding to collagens I-VI. In the "closed" (wild-type) conformation, the α(L)I and α(M)I domains bound with low avidity to their primary ligands, and the interaction with collagens was also very weak. Gain-of-function mutations α(L) I306G, α(L) K287C/K294C and α(M) I316G are considered to mimic "open", activated αI domains. The binding of these activated αI domains to the primary ligands was clearly stronger and they also recognized collagens with moderate avidity (K(d)400 nM). After activation, the αLI domain favored collagen I (K(d )≈ 80 nM) when compared to collagen IV. The integrin αXI domain acted in a very different manner since already in native, wild-type form it bound to collagen IV and iC3b (K(d) ≈ 200-400 nM). Antibodies against αXβ2 and αMβ2 blocked promyelocytic leukemia cell adhesion to the collagenous GFOGER motif, a binding site for the β1 integrin containing collagen receptors. In brief, leukocyte β2 integrins may act as collagen receptors in a heterodimer specific manner.