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Publication : Binding of lymphoid chemokines to collagen IV that accumulates in the basal lamina of high endothelial venules: its implications in lymphocyte trafficking.

First Author  Yang BG Year  2007
Journal  J Immunol Volume  179
Issue  7 Pages  4376-82
PubMed ID  17878332 Mgi Jnum  J:152361
Mgi Id  MGI:4358051 Doi  10.4049/jimmunol.179.7.4376
Citation  Yang BG, et al. (2007) Binding of lymphoid chemokines to collagen IV that accumulates in the basal lamina of high endothelial venules: its implications in lymphocyte trafficking. J Immunol 179(7):4376-82
abstractText  Certain lymphoid chemokines are selectively and constitutively expressed in the high endothelial venules (HEV) of lymph nodes and Peyer's patches, where they play critical roles in the directional migration of extravasating lymphocytes into the lymphoid tissue parenchyma. How these chemokines are selectively localized and act in situ, however, remains unclear. In the present study, we examined the possibility that basal lamina-associated extracellular matrix proteins in the HEVs are responsible for retaining the lymphoid chemokines locally. Here we show that collagen IV (Col IV) bound certain lymphoid chemokines, including CCL21, CXCL13, and CXCL12, more potently than did fibronectin or laminin-1, but it bound CCL19 and CCL5 only weakly, if at all. Surface plasmon resonance analysis indicated that Col IV bound CCL21 with a low nanomolar K(D), which required the C-terminal region of CCL21. Col IV can apparently hold these chemokines in their active form upon binding, because the Col IV-bound chemokines induced lymphocyte migration efficiently in vitro. We found by immunohistochemistry that Col IV and CCL21, CXCL13, and CXCL12 were colocalized in the basal lamina of HEVs. When injected s.c. into plt/plt mice, CCL21 colocalized at least partially with Col IV on the basal lamina of HEVs in draining lymph nodes. Collectively, our results suggest that Col IV contributes to the creation of a lymphoid chemokine-rich environment in the basal lamina of HEVs by binding an array of locally produced lymphoid chemokines that promote directional lymphocyte trafficking from HEVs into the lymphoid tissue parenchyma.
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