The CXC chemokine MIP-2 stimulates neutrophil mobilization from the rat bone marrow in a CD49d-dependent manner.
The acute release of neutrophils from the bone marrow is a critical step in their trafficking to sites of inflammation. This process is stimulated by systemically acting inflammatory mediators, such as the CXC chemokines. In this study we have used a novel in situ perfusion system of the rat femoral bone marrow to directly investigate the role of specific adhesion molecules in chemokine-stimulated neutrophil mobilization. We show here that neutrophils mobilized in response to rat macrophage inflammatory protein-2 (MIP-2) shed L-selectin and expressed significantly higher levels of CD11b and CD49d. However, inhibition of L-selectin sheddase activity with KD-IX-73-4 had no effect on the number of neutrophils mobilized in response to rat MIP-2. Blockade of CD18, using a neutralizing monoclonal antibody (mAb), did not inhibit neutrophil mobilization but unexpectedly increased the rate and number of neutrophils released from the bone marrow in response to chemokine, suggesting that CD18 could play a role in neutrophil retention within the bone marrow. Blockade of CD49d using either a selective mAb or a specific antagonist resulted in a dramatic inhibition (> 75%) of the chemokine-stimulated neutrophil mobilization from the bone marrow. These data reveal contrasting roles for CD18 and CD49d in the retention and release of neutrophils from the bone marrow.
Burdon
Peter C E
PC
Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Sir Alexander Fleming Bldg, Exhibition Rd, South Kensington, London SW7 2AZ, United Kingdom.
Martin
Coralie
C
Rankin
Sara M
SM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D039481:CD11b Antigen / Q000096:biosynthesis; D018821:CD18 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000008:administration & dosage* / Q000378:metabolism; D004151:Dipeptides / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006877:Hydroxamic Acids / Q000008:administration & dosage; D007249:Inflammation / Q000378:metabolism; D039441:Integrin alpha4 / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D018821:CD18 Antigens; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D004151:Dipeptides; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C099147:KD-IX 73-4; D019041:L-Selectin; D039441:Integrin alpha4