title: Migration across the sinusoidal endothelium regulates neutrophil mobilization in response to ELR + CXC chemokines.
abstract: An increase in circulating neutrophils is a characteristic feature of many inflammatory reactions and is a result of the rapid mobilization of neutrophils from the bone marrow, driven by inflammatory mediators, including the ELR + CXC chemokines. In this paper, using a combination of light and electron microscopy and an in situ perfusion system of the rat femoral bone marrow, we examined this mobilization process in detail. We show that mobilization of neutrophils stimulated by the CXC chemokine, rat MIP-2, involves neutrophil migration from the haematopoietic compartment of the bone marrow across the bone marrow sinusoidal endothelium via a transcellular route. The critical role of the bone marrow sinusoidal endothelium in regulating neutrophil mobilization was demonstrated by artificially disrupting the bone marrow endothelial barrier by treatment with cytochalasin D, which results in the non-selective release of leucocytes from the bone marrow. In contrast, inhibiting the activity of p38 mitogen-activated protein kinase, inhibited both MIP-2 stimulated chemotaxis of bone marrow neutrophils in vitro and neutrophil mobilization in situ while, a broad spectrum matrix metalloproteinase inhibitor, BB94, had no effect on neutrophil mobilization. These results support the hypothesis that neutrophil migration drives their mobilization and highlights the function of the sinusoidal endothelium in regulating this process.
authors.affiliation: Leukocyte Biology Section, NHLI Division, Faculty of Medicine, Imperial College, South Kensington, London, UK.
authors.forename: Peter C E
authors.initials: PC
authors.lastname: Burdon
authors.forename: Coralie
authors.initials: C
authors.lastname: Martin
authors.forename: Sara M
authors.initials: SM
authors.lastname: Rankin
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D002465:Cell Movement; D054426:Chemokine CXCL2 / Q000494:pharmacology*; D019743:Chemokines, CXC / Q000494:pharmacology*; D015638:Cytochalasin D / Q000494:pharmacology; D004727:Endothelium; D008213:Lymphocyte Activation; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D009504:Neutrophils / Q000502:physiology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013876:Thiophenes / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D061965:Matrix Metalloproteinase Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D013876:Thiophenes; D015638:Cytochalasin D; D010649:Phenylalanine; C080985:batimastat; D048051:p38 Mitogen-Activated Protein Kinases