Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.0908576 on May 4, 2009

Published online before print May 4, 2009
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(Journal of Leukocyte Biology. 2009;86:609-615.)
© 2009 Society for Leukocyte Biology

Requirement of HMGB1 for stromal cell-derived factor-1/CXCL12-dependent migration of macrophages and dendritic cells

Lara Campana*, Lidia Bosurgi{dagger}, Marco E. Bianchi{ddagger}, Angelo A. Manfredi{dagger} and Patrizia Rovere-Querini*,1

* Innate Immunity and Tissue Remodeling Unit,
{dagger} Clinical Immunology Unit, and
{ddagger} Chromatin Dynamics Unit, H San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milano, Italy

1. Correspondence: Innate Immunity and Tissue Remodeling Unit, H. San Raffaele Scientific Institute, via Olgettina 58, Milano 20132, Italy. E-mail: rovere.patrizia{at}hsr.it

ABSTRACT

HMGB1 finely tunes the function of DCs, thus influencing their maturation program and eventually the establishment of adaptive, T cell-dependent immune responses. Moreover, it promotes the up-regulation of receptors for lymph node chemokines, regulates the remodeling of the cytoskeleton of migrating cells, and sustains their journey to secondary lymphoid organs via a RAGE-dependent pathway. The inflammatory properties of HMGB1 depend at least partially on the ability to complex with soluble moieties, including nucleic acids, microbial products, and cytokines. Here, we show that bone marrow-derived mouse DCs release HMGB1 during CXCL12-dependent migration in vitro. Macrophages share this property, suggesting that it may be a general feature of CXCL12-responsive leukocytes. The chemotactic response to rCXCL12 of DCs and macrophages abates in the presence of the HMGB1 antagonist BoxA. HMGB1 secreted from DCs and macrophages binds to CXCL12 in the fluid phase and protects the chemokine conformation and function in a reducing environment. Altogether, our data indicate that HMGB1 release is required for CXCL12 ability to attract myeloid-derived cells and reveal a functional interaction between the two molecules that possibly contributes to the regulation of leukocyte recruitment and motility.

Key Words: cell trafficking • chemotaxis • inflammation • leukocytes recruitment • DAMPs