STUDIES ON THE MECHANISM OF HAEMOPOIETIC STEM CELL (CFUs) MOBILIZATION

Abstract

A variety of substances can mobilize haemopoietic stem cells (CFUs) into the peripheral blood. In this study the involvement of the complement system in the mobilization process was investigated. Pretreatment of mice with the complement‐activating factor of cobra venom (CoF), which lowered the serum C3 levels to 10–25% of the normal value, could completely prevent CFUs mobilization induced by high doses of CoF, endotoxin (ET) from Salmonella typhosa, inulin, zymosan and the proteolytic enzymes proteinase and trypsin. On the other hand, mobilization induced by the polyanions dextran sulphate and the copolymer of polymethacrylic acid and styrene could not be prevented, or at least affected only slightly. There appears to be a relationship between the extent of decomplementation by CoF and the extent of CFUs mobilization induced by ET. The results indicate that certain agents mobilize CFUs via the complement system, whereas other agents induce CFUs mobilization independent of the availability of complement components.

Mobilization of Hematopoietic Stem/Progenitor Cells: General Principles and Molecular Mechanisms

“…Moreover, a variety of mediators have been associated with mobilization that seemingly have very little in common, and where the molecular mechanics are sometimes poorly defined. These include sympathomimetics (77, 78), cannabinoid receptor agonists (79), complement (52, 53), elevated lipoprotein levels (80), defibrotide (81), glycosaminoglycans (82), and endotoxin (83). None of these have gained any clinical relevance, but the abundance of mobilizing agents indicates the precariousness of the equilibrium between marrow retention and egress, and may in the future support the rational development of mobilizing strategies for poorly mobilizing patients, or for individuals who are intolerant to G-CSF.…”

Transplantation studies in C3-deficient animals reveal a novel role of the third complement component (C3) in engraftment of bone marrow cells

“…Studies reported over 20 years ago first showed that depletion of C in mice with cobra venom (CoF), which lowered serum C3 levels to 10-25% of normal values, completely prevented CFU-S mobilization induced by endotoxin. 52 Our recent report demonstrated that mice deficient in either C3 or C3aR were more sensitive to mobilization by G-CSF than were WT mice, and that mobilization in WT animals could be increased by employing a C3aR antagonist. 38 Moreover, an anti-CR3 mAb has been reported to enhance mobilization in mice, suggesting an involvement of the iC3b-CR3 axis in addition to the C3a-C3aR axis.…”

Mobilisierung hämatopoietischer Stammzellen

“…Die Fähigkeit zirkulierender hämatopoietischer Stammzellen zum Repopulieren entfernter Knochenmarksregionen durch hämatogene Aussaat ist direkt belegt durch Teilkörperbestrahlungs-und Parabiose-Experimente in der Maus [23][24][25][26][27][28]. Eine Vielzahl von Stimuli, darunter exogene hämatopoietische Wachstumsfaktoren [29], Chemokine [30][31][32][33][34][35][36] und Chemokinrezeptor-Antagonisten [37,38], der myeloische Rebound nach zytoreduktiver Chemotherapie [39,40], Integrinrezeptorblocker [41][42][43], bakterielle Toxine [44][45][46][47], aber auch körperliche Anstrengung [48,49], Tageszeit [50][51][52], adrenerge Signale des autonomen Nervensystems [52][53][54][55][56] oder nicht primär hämatologische pathologische Zustände wie Entzündung [44,57], Gewebeschädigung [58], Komplementaktivierung [59,60], Gerinnungsaktivierung [61], können erhöhte Zahlen zirkulierender Stammzellen induzieren. [30,32,33,…”