Modulation of leukocyte migration in mesenteric interstitium.

Intravital videomicroscopy was used to monitor the migration of leukocytes in rat mesenteric interstitium following exposure of the mesentery to either N-formylmethionyl-leucyl-phenylalanine (FMLP), leukotriene B4 (LTB4), platelet-activating factor (PAF), or ischemia-reperfusion (I-R). All inflammatory stimuli resulted in interstitial migration rates that were higher than those measured in unstimulated extravasated leukocytes. The median migration rate of cells stimulated with FMLP was significantly higher than those observed during superfusion with either LTB4 or PAF or following exposure to I-R. The enhanced leukocyte migration rates elicited by I-R were not attenuated by treatment with PAF- and LTB4-receptor antagonists, suggesting that these lipid mediators are not the inflammatory mediators responsible for I-R-induced leukocyte migration. Additional experiments revealed that the rate of leukocyte migration associated with FMLP stimulation was not significantly altered by either inhibitors of neutrophilic elastase and cathepsin G, a monoclonal antibody directed against the leukocyte adhesion glycoprotein CD11/CD18, or by altering interstitial hydration. This in vivo model provides a useful new approach for defining the factors that modulate leukocyte migration within the extravascular compartment.