Effect of vasoactive agents on polymorphonuclear leukocyte emigration in vivo.

During many acute inflammatory reactions, neutrophil infiltration, probably initiated by locally generated chemotactic stimuli, is often accompanied by simultaneous increases in vascular permeability and blood flow. Although mediators such as bradykinin, histamine, and prostaglandins increase permeability and/or blood flow, usually they do not induce neutrophil infiltration. This study investigated the possibility that such mediators may, however, modulate neutrophil infiltration initiated by chemotactic stimuli in vivo. Neutrophil infiltration, vascular permeability, and blood flow in skin sites in rabbits were quantitated simultaneously with 51Cr-labeled rabbit blood leukocytes, 125I-albumin, and 86RbCl, respectively. The intradermal injection of prostaglandins E1 (0.25 microgram), E2 (0.5 microgram), or F2 alpha (1 microgram) into sites which had previously been injected with chemotactic stimuli, such as zymosan-activated plasma, zymosan, or N-formyl-methionyl-leucyl-phenylalanine, markedly enhanced the rate of neutrophil influx induced by the latter stimuli. The injection of histamine (0.25 microgram), bradykinin (0.02 microgram), or compound 48/80 (100 microgram) similarly enhanced the neutrophil infiltration induced by zymosan-activated plasma. None of the vasoactive agents, when injected into a normal skin, caused neutrophil infiltration. Simultaneous permeability and blood flow measurements suggested that an increase either in vascular permeability or in local blood flow may enhance the degree of neutrophil infiltration of the tissues during chemotactic stimulus-mediated inflammation.