Immune cell recruitment to inflammatory loci is impaired in mice deficient in basement membrane protein laminin alpha4.

For leukocytes to penetrate the vessel wall, they need to interact sequentially with the endothelial lining and the perivascular BM. The matrix protein laminin-411 is a major constituent of the vascular BM. The laminin alpha4 chain is a component of laminin-411 and has structural and signaling functions. Here, we addressed the role of BM laminin alpha4 in leukocyte recruitment to inflammatory loci. We used several recruitment models in Lam4(-/-) and WT mice to determine whether lack of laminin-411 in the perivascular BM influences extravasation of inflammatory cells. Recruitment of all major leukocyte subsets (neutrophils, monocytes, and lymphocytes) was reduced in Lam4(-/-) mice compared with WT. With the use of intravital microscopy, we concluded that this decrease was a result of impaired diapedesis through the vessel wall, as neither leukocyte adhesion to the endothelial lining nor migration in extravascular tissue was hampered in Lam4(-/-) mice. Collectively, our data suggest a reduced ability of immune cells to penetrate the vessel wall in mice deficient in laminin alpha4.