Leukocyte subpopulations and arteriogenesis: specific role of monocytes, lymphocytes and granulocytes.
OBJECTIVE
Circulating leukocytes play a crucial role during arteriogenesis. However, known pro-arteriogenic compounds (MCP-1, GM-CSF) acting via monocytic pathways also exert positive effects on granulocytes and lymphocytes. The role of these two cell types in arteriogenesis remains yet to be clarified, which was the aim of the current study.


METHODS
Ninety New Zealand White Rabbits received either phosphate buffered saline (PBS), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), neutrophil activating protein-2 (NAP-2) or lymphotactin (Ltn) via osmotic minipumps after unilateral femoral artery ligation. In vitro stimulation and in vivo assessment of chemoattraction confirmed cell-specific action of the compounds in rabbits. Arteriogenesis was evaluated by angiography and collateral conductance measurements using fluorescent microspheres. Quantitative immunohistology was used to quantify transmigrated leukocyte subtypes after infusion of the factors.


RESULTS
MCP-1 infusion attracts monocytes and granulocytes, whereas IL-8 attracts all three cell types albeit monocytes to a significantly lower degree than MCP-1. NAP-2 and lymphotactin selectively attract granulocytes, respectively, lymphocytes. Of the tested cytokines, only MCP-1 stimulates arteriogenesis, as assessed by collateral conductance measurements ((ml/(min 100 mmHg)): PBS, 50.70+/-5.15; MCP-1, 216.30+/-12.30; IL-8, 58.91+/-5.56; NAP-2, 66.83+/-8.72; Ltn, 52.80+/-5.37) and angiographic findings.


CONCLUSIONS
This study for the first time provides evidence that not granulocytes or T-lymphocytes but monocytes are the key mediators of arteriogenesis.
Hoefer
Imo E
IE
Research Group for Experimental and Clinical Arteriogenesis, Department of Cardiology, University of Freiburg, Germany. i.hoefer@azu.nl
Grundmann
Sebastian
S
van Royen
Niels
N
Voskuil
Michiel
M
Schirmer
Stephan H
SH
Ulusans
Susann
S
Bode
Christoph
C
Buschmann
Ivo R
IR
Piek
Jan J
JJ
D000818:Animals; D001158:Arteries / Q000276:immunology; D018932:Chemokine CCL2 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects / Q000276:immunology*; D006098:Granulocytes / Q000502:physiology; D016209:Interleukin-8 / Q000494:pharmacology; D007962:Leukocytes / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology; D008222:Lymphokines / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000276:immunology*; D010455:Peptides / Q000494:pharmacology; D011817:Rabbits; D012795:Sialoglycoproteins / Q000494:pharmacology; D001620:beta-Thromboglobulin
D018932:Chemokine CCL2; D016209:Interleukin-8; D008222:Lymphokines; C061615:PPBP protein, human; D010455:Peptides; D012795:Sialoglycoproteins; D001620:beta-Thromboglobulin; C018997:lymphotactin