Mechanisms underlying acute mast cell-induced leukocyte rolling and adhesion in vivo.
It has been proposed that a primary detector mechanism for tissue infection or injury may be the mast cell that releases agents that recruit leukocytes to the appropriate site at risk. The objective of this study was to evaluate the early mechanisms involved in mast cell-induced leukocyte recruitment. We used intravital microscopy to visualize leukocyte-rolling flux and adhesion in single 25 to 40 microns venules in mesenteric preparations that were treated with the mast cell-degranulating agent, compound 48/80 (CMP 48/80). Superfusion of the rat mesentery with CMP 48/80 caused a dose-dependent rise in the number of rolling and adherent cells, events significantly reduced by: 1) mast cell stabilizers, ketotifen, or cromolyn, and 2) chronic treatment with CMP 48/80 to deplete mast cell constituents. The increase in leukocyte flux associated with CMP 48/80 was blocked by diphenhydramine (H1-receptor antagonist) and an anti-P-selectin Ab (PB1.3), but not by the 5-lipoxygenase inhibitor, MK 886. The reduction in the flux of rolling leukocytes translated into fewer adherent leukocytes with diphenhydramine or PB1.3. The CMP 48/80-induced rise in leukocyte adhesion, but not leukocyte flux, was reduced by the platelet-activating factor (PAF)-receptor antagonist (WEB 2086) and an anti-CD18 Ab (CL26). MK 886 did not prevent the increased leukocyte adhesion. In vitro data revealed that mast cell-derived PAF induced essentially all of the leukocyte adhesion to endothelium or protein-coated plastic. These data suggest that mast cell degranulation induces P-selectin-dependent leukocyte rolling and CD18-dependent leukocyte adhesion via histamine and PAF, respectively.
Gaboury
J P
JP
Immunology Research Group, University of Calgary Medical Center, Alberta, Canada.
Johnston
B
B
Niu
X F
XF
Kubes
P
P
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015550:Cell Degranulation / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D006632:Histamine / Q000502:physiology; D007962:Leukocytes / Q000502:physiology*; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D003189:p-Methoxy-N-methylphenethylamine
D015289:Leukotrienes; D010972:Platelet Activating Factor; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine