Spontaneous and rapid reexpression of functional CXCR4 by human steady-state peripheral blood CD34+ cells

Abstract

Although only 5% of steady-state peripheral blood (PB) CD34+ cells were found to express chemokine receptor CXCR4, 45% of the cells became CXCR4+ after incubation at 37 degrees C for 4 hours. In contrast, there were no remarkable differences between PB CD34+ cells before and after the 37 degrees C incubation in their expression of selectin ligand, VLA-4, and VLA-5 or in their affinity for VCAM-1 or fibronectin. This increase in CXCR4 expression level was inhibited by the addition of brefeldin A, actinomycin D, or cycloheximide. When PB CD34+ cells with CXCR4 expression levels enhanced by a 4-hour preincubation at 37 degrees C or bone marrow (BM) CD34+ cells were exposed overnight to stromal cell-derived factor 1 (SDF-1), the expression levels of CXCR4 were greatly reduced, and when SDF-1 was removed, CXCR4 levels were thereafter up-regulated. The reexpressed CXCR4 was able to elicit integrin-dependent migration of hematopoietic progenitor cells. There was no difference in the severe combined immunodeficient mouse repopulating cell activity between PB CD34+ cells with and cells without a 37 degrees C preincubation.

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

“…The seemingly counterintuitive increase of SDF-1-induced chemotaxis of MPB CFU-C despite down-regulated CXCR4 was previously reported, but not explained. [24,27,47,52,53] Since CXCR4 is reexpressed on HPC after brief cytokine exposure [54,55] or early after transplantation [47], the physiologic relevance of down-regulated CXCR4 on MPB HPC found in vitro is not clear, as it may not represent the status of the cells exposed to the in vivo environment in the conditioned host. Furthermore, the correlation between CXCR4 expression and in vitro migration may not be straight forward.…”

G-CSF and neuroprotection: a therapeutic perspective in cerebral ischaemia

“…Cerebral ischaemia causes an increase in CXCR4 (CXC chemokine receptor 4) receptor ligand SDF-1 (stromal-derived factor-1) expression in regions adjacent to the infarcted area, indicating that SDF-1 within the brain could be a chemoattractant for peripheral CD34 + CXCR4 + cells [18]. A marked increase in expression of CXCR4 was detected in the ischaemic region of G-CSF-treated rats compared with the contralateral nonischaemic side or normal healthy controls [19], suggesting that haemopoietic CD34 + cells undergo directional migration towards SDF-1 in regions adjacent to the infarcted area.…”

“…G-CSF-treated experimental models showed better functional recoveries from 2 weeks to 5 weeks after ischaemia compared with the cerebral ischaemia-only controls [6,9]. G-CSF given in the subacute phase (days [11][12][13][14][15][16][17][18][19][20] effectively improved not only motor performance but also higher brain function, compared with acute-phase treatment (days 1-10) [10]. Our results indicate that subcutaneous injection of G-CSF (10 µg/kg per day) for 5 days decreases mortality rate, reduces infarction volume and improves neurological behaviour after cerebral ischaemia (Figure 1).…”

O G-CSF na terapia do acidente vascular cerebral

“…A mobilização de células precursoras é menos problemática em todos os aspectos quando comparada com o transplante, e possui uma sólida base científica. 10,[13][14][15][16][17][18][19][20][21][22] O G-CSF como agente mobilizador e protetor Dentre os vários agentes mobilizadores de células precursoras conhecidos atualmente, o G-CSF tem recebido considerável atenção. O G-CSF é uma glicoproteína com 19,6 kilodaltons e membro da família de citocinas de fatores de crescimento, descrita há mais de vinte anos, inicialmente como uma indutora da diferenciação da célula leucêmica monocitária WEHI-3B, 23,24 e clonada por Nakata.…”